Reversible 3-D Cell Culture Gel Invented

Thixotropic three-dimensional gel to revolutionize cell culture
Sunday, 28 September 2008

Singapore's Institute of Bioengineering and Nanotechnology (IBN), which celebrates its fifth anniversary this year, has invented a unique user-friendly gel that can liquefy on demand, with the potential to revolutionize three-dimensional (3D) cell culture for medical research.

As reported in Nature Nanotechnology, IBN's novel gel media has the unique ability to liquefy when it is subjected to a moderate shear force and rapidly resolidifies into a gel within one minute upon removal of the force. This phenomenon of reverting between a gel and a liquid state is known as thixotropy.

IBN's thixotropic gel is synthesized from a nano-composite of silica and polyethylene glycol (PEG) under room temperature, without special storage conditions. This novel material facilitates the safe and convenient culture of cells in 3D since cells can be easily added to the gel matrix without any chemical processes.

According to IBN Executive Director Jackie Y. Ying, Ph.D.:

"Cell culture is conventionally performed on a flat surface such as glass slides. It is an essential process in biological and medical research, and is widely used to process cells, synthesize biologics and develop treatments for a large variety of diseases.”

"Cell culture within a 3D matrix would better mimic the actual conditions in the body as compared to the conventional 2D cell culture on flat surfaces. 3D cell culture also promises the development of better cell assays for drug screening," Dr. Ying added.

Another key feature of IBN's gel is the ease with which researchers can transfer the cultured cells from the matrix by pipetting the required amount from the liquefied gel.

Unlike conventional cell culture, trypsin is not required to detach the cultured cells from the solid media. As trypsin is an enzyme that is known to damage cells, especially in stem cell cultures, the long-term quality and viability of cells cultured using IBN's thixotropic gel would improve substantially without the exposure to this enzyme.

Researchers are also able to control the gel's stiffness, thus facilitating the differentiation of stem cells into specific cell types.

"Ways to control stem cell differentiation are important as stem cells can be differentiated into various cell types. Our gel can provide a novel method of studying stem cell differentiation, as well as an effective new means of introducing biological signals to cells to investigate their effect in 3D cultures," said Shona Pek, IBN Research Officer.

Andrew Wan, Ph.D., IBN Team Leader and Principal Research Scientist, said:

“Another interesting property of the gel is its ability to support the extracellular matrix (ECM) secretions of cells. Gel stiffness is modulated by ECM secretions, and can be used to study ECM production by cells responding to drug treatments or disease conditions.”

"The thixotropic gel may then provide new insights for basic research and drug development," Dr. Wan added.

About Institute of Bioengineering and Nanotechnology (IBN):
IBN, a member of Singapore's Agency for Science, Technology and Research (A*STAR), was established in 2003.

Massachusetts Institute of Technology (MIT) Professor Jackie Yi Ru Ying, 42, was hand-picked by then A*STAR Chairman Philip Yeo to lead the institute as its Executive Director. She has been on MIT's Chemical Engineering faculty since 1992, and was promoted to professor in 2001. She is among the youngest to be promoted to this rank at MIT. Under her direction, IBN conducts research at the cutting-edge of bioengineering and nanotechnology.

Its programs are geared towards linking multiple disciplines across all fields in engineering, science and medicine to produce research breakthroughs that will improve healthcare and our quality of life.

IBN's research activities are focused in the following areas:

• Drug and Gene Delivery, where the controlled release of various therapeutics involve the use of functionalized polymers and hydrogels for targeting diseased cells and organs, or for responding to specific biological stimuli.
• Cell and Tissue Engineering, where biomimicking materials, stem cell technology and bioimaging are combined to develop novel approaches to regenerative medicine and artificial organs.
• Pharmaceuticals Synthesis and Nanobiotechnology, which encompass the efficient catalytic synthesis of chiral pharmaceuticals, and new materials for sustainable technology and alternative energy generation.
• Biosensors and Biodevices, which involve nanotechnology and microfabricated platforms for the detection and treatment of diseases, and the synthesis and screening of biologics.

IBN's innovative research is aimed at creating new knowledge and intellectual properties in the emerging fields of bioengineering and nanotechnology, to attract top-notch researchers and business partners to Singapore.

Since 2003, IBN researchers have produced a total of 436 papers published/in press, of which 177 were published in journals with impact factor greater than 3. IBN's work on hybrid magnetic-fluorescent nanoparticles, published in the Journal of the American Chemical Society in 2005, has received over 100 citations in three years.

IBN also plays an active role in technology transfer and spinning off companies, linking the research institute and industrial partners to other global institutions. As of July 2008, IBN has filed 578 patent applications on its inventions and the Institute is currently looking for partners for collaboration and commercialization of its portfolio of technologies.

IBN's current staff strength totals about 170 scientists, engineers and doctors. With its multinational and multidisciplinary research staff, the institute is geared towards generating new biomaterials, devices, systems, equipment and processes to boost Singapore's economy in the fast-growing biomedical sector.

IBN is also committed to nurturing young minds, and the institute acts as a training ground for PhD students and undergraduates. In October 2003, IBN initiated a Youth Research Program to open its doors to university students, as well as students and teachers from various secondary schools and junior colleges. It has since reached out to more than 23,000 students and teachers from over 190 local and overseas schools and institutions.

In 2008, IBN celebrates 5 years of innovative research.

Reference:
A Thixotropic Nanocomposite Gel for Three-Dimensional Cell Culture
Y. Shona Pek, Andrew C. A. Wan, Asha Shekaran, Lang Zhuo & Jackie Y. Ying
Nature Nanotechnology, Published online: 28 September 2008, doi:10.1038/nnano.2008.270
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Why US Standing In the World Are Declining

A short, provocative, outside view on US political future
Sunday, 28 September 2008

When will you, American’s, realize that the 700-billion-dollar-bailout is related to the trillions of dollars in war spending Bush’s has demanded during his eight years in power! Moreover, all of them borrowed from the Chinese and Saudi’s and other oil rich dictators!

China has used the last seven years to prepare for the Olympics, its presence in space and becoming the world’s production house for ‘everything’!

During the same time, the US has shadow-fought al-Qaida in Afghanistan and Iraq, pretty much as Don Quixote de la Mancha was fighting windmills. In addition, Bush still did not gain any oil revenue’s from the Iraqi oil fields as he expected!

While China was building new subways, air terminals, highways, high-speed railways, parks and space rockets for manned flights, paid by its domestic production, the US was building metal detectors and UAV’s and poorly armoured vehicles for its military personnel, paid by borrowed money.

What else could you expect, than the present meltdown of your economic system, and finally loosing your status as super-power. Soviet Union needed a star-wars race to be exposed as the bankrupt economy and political system it was, US only needed two high-rise buildings to fall.


ZenMaster

Gene Therapy Shrink Brain Tumours

Animal study supports creating zone of resistance in surrounding normal tissue.
Thursday, 25 September 2008

Massachusetts General Hospital (MGH) researchers are investigating a new approach to gene therapy for brain tumours – delivering a cancer-fighting gene to normal brain tissue around the tumour to keep it from spreading. An animal study published in the journal Molecular Therapy, the first to test the feasibility of such an approach, found that inducing mouse brain cells to secrete human interferon-beta suppressed and eliminated growth of human glioblastoma cells implanted nearby.

"We had hypothesized that genetically engineering normal tissue surrounding a tumour could create a zone of resistance – a microenvironment that prevents the growth or spread of the tumour," says Miguel Sena-Esteves, PhD, of the MGH Neuroscience Center, the study's senior author.

"This proof of principle study shows that this could be a highly effective approach, although there are many additional questions that need to be investigated."

Glioblastoma is the most common and deadly form of brain tumour. Human clinical trials of other gene therapies have not significantly reduced tumour progression. One problem has been that patients' immune systems target the viral vectors used to deliver cancer-eliminating genes. Another issue has been inefficient gene delivery, due in part to the inherent cellular diversity found within an individual patient's tumour as well as among tumours from different patients. In addition, if tumour cells are successfully induced to express an anticancer protein, production of that protein will drop as the tumour dies, allowing any cells that did not receive the gene to resume growing. In the current study the MGH team examined whether expression of a therapeutic gene in normal brain cells could form a stable and effective anti-tumour reservoir.

The researchers first pre-treated immune-deficient mice by delivering a gene for human interferon-beta – a protein being tested against several types of cancer – into the animals' brains using adeno-associated virus vectors known to effectively deliver genes to neurons in the brain without the immune reaction produced by other vectors. Two weeks later, human glioblastoma cells were injected into the same or adjacent areas of the animal's brains. After only four days, mice expressing interferon-beta had significantly smaller tumours than did a control group pre-treated with gene-free vector. Two weeks after the glioblastoma cells were introduced, the tumours had completely disappeared from the brains of the gene-therapy-treated mice.

Several additional experiments verified that the anti-tumour effect was produced by expression of interferon-beta in normal tissue. The same tumour growth suppression was seen when the genes were delivered to one side of the brain and tumour cells were injected into the other. Using a specialized vector that allows genes to be expressed only in neuronal cells and not the glial cells from which glioblastomas originate also produced similar results. While other gene therapy studies that have induced tumour regression in mouse models required several vector injections, these experiments were able to suppress growth and eliminate the implanted tumour with a single injection of the interferon-beta-encoding vector, underscoring the approach's effectiveness.

"These results are particularly important as we build on our understanding of the microenvironments that allow tumours to grow and spread," explains Sena-Esteves, an assistant professor of Neurology at Harvard Medical School.

"The therapeutic principle of genetically engineering normal brain tissue could be used to manipulate proteins required for that microenvironment, preventing tumours from migrating within the patient’s brain and escaping other therapies." The same zone-of-resistance approach could also be applied to the treatment of other solid tumours, he notes.

Since interferon-beta treatment is known to have side effects, it will be important to identify any toxicity caused by long-term secretion of the protein in the brain and develop preventive strategies, such as turning off the introduced genes. Next, the MGH team is planning to test this strategy on glioblastomas that occur naturally in dogs, which could not only generate additional data supporting human trials but also develop veterinary treatments for canine patients.

Reference:
Preventing Growth of Brain Tumors by Creating a Zone of Resistance
Casey A Maguire, Dimphna H Meijer, Stanley G LeRoy, Laryssa A Tierney, Marike LD Broekman, Fabricio F Costa, Xandra O Breakefield, Anat Stemmer-Rachamimov and Miguel Sena-Esteves
Molecular Therapy (2008) 16 10, 1695–1702 doi:10.1038/mt.2008.168
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Novel Inhibitor of Human microRNA

Discovery points to new avenue for cancer treatment
Thursday, 25 September 2008

Scientists at The Wistar Institute and their colleagues have identified, for the first time, a molecule that can regulate microRNAs – short strands of RNA that play a vital role in gene expression and are closely associated with cancer. The discovery points the way to the development of a new generation of cancer drugs.

The research team identified a small molecule that blocks the pathway of a particular miRNA, called miR-21, which is implicated in brain cancer, as well as lung, colon, breast, and ovarian cancer. With further development, the molecule has the potential to boost patient response to existing chemotherapies, as well as to become a stand-alone cancer drug, says Wistar's Qihong Huang, M.D., Ph.D., co-senior author of the study.

Although miRNAs were discovered less than two decades ago, their importance in regulating human development and disease is already clear. While the human genome is thought to contain 800 to 1,000 miRNAs, only a few hundred have been described.

Thus, miRNAs represent a largely unexplored class of targets for the development of therapeutics and diagnostics, says Huang, an assistant professor in Wistar's Molecular and Cellular Oncogenesis Program.

"This is a totally novel target," he says.

"It's very understudied, and still in its infancy, but its potential is tremendous. Because miRNAs have the ability to shut down genes and prevent their expression, they may ultimately provide a target for therapies that are more selective than conventional chemotherapy drugs and have fewer side effects."

Alexander Deiters, Ph.D., of North Carolina State University, co-directed the study.

In regulating the molecular mechanisms behind gene expression, miRNAs can control the way in which whole chromosomes, or regions of chromosomes, are activated or deactivated. They are thought to directly regulate the expression of at least 30 percent of all human protein-encoding genes.

miRNAs regulate protein synthesis by binding to the messenger RNAs that provide the recipe for protein construction. In doing so, the miRNAs repress the relevant protein's production. Misregulation of miRNAs can result in genes being over- or under-expressed, leading to cancer and other diseases.

Huang notes that one sizeable hurdle in harnessing the power of miRNAs is getting "the right molecule into the right place at the right time" to regulate their function.

"In terms of developing therapeutic agents for cancer, for example, we need to identify small molecules that can get into the bloodstream and get into the cells," he says.

"The problem is, to date, no one had been able to show that such miRNA inhibitors exist."

Huang and his colleagues developed a method to identify inhibitors of miRNA pathways in live human cells. The researchers created screening assays, or tests, to look for small molecules or compounds that selectively repress miRNA. They selected miR-21 as the target agent due to its documented role in preventing cell death – thereby allowing the unchecked cell proliferation associated with cancer – and its elevated levels in various cancers.

The team designed an assay that contained the DNA binding sequence complementary to miR-21, bound to luciferase, the protein fireflies use to create light. Because miRNAs inhibit protein production, when miR-21 is functioning normally, it binds with the complementary sequence and inhibits the translation of luciferase, thus reducing the intensity of the light signal.

"The idea was that when we add small molecules that inhibit the function of miR-21, the light signal will increase," Huang says.

The scientists then screened a "library" of 1,000 compounds and found one molecule that inhibited miR-21 in the assay. The molecule, diazobenzene 2, decreased miR-21 levels by 80 percent and produced a nearly five-fold increase in the intensity of the light signal from the firefly protein. Groups of control cells and untreated cells showed no such signal when treated with the small-molecule inhibitor.

The findings were published in the September 15 issue of the scientific journal Angewandte Chemie.

Preliminary data from the researchers' ongoing studies suggest that the inhibitor could be used in combination with other chemotherapy drugs to provide a synergistic effect, Huang says. The researchers also will evaluate its potential as a stand-alone cancer drug. Huang and his colleagues are now conducting studies in mice to assess the inhibitor's effectiveness against brain, breast, and colon tumours, and they are working to modify the molecule to make it even more efficient.

The screening test developed by the researchers provides a unique tool that can be used to advance investigations of miRNAs and their involvement in various diseases, Huang says.

"The cell-based assay that we have established can potentially be used to screen for additional small-molecule inhibitors that can block miRNA," he notes.
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Cloned Pigs with Cystic Fibrosis

Model to mimic human disease
Thursday, 25 September 2008

In a first, researchers at the University of Iowa and the University of Missouri (MU) have developed a pig model for Cystic Fibrosis (CF) that appears to closely mimic the disease in human infants. The striking similarities between disease manifestations in the CF piglets and human newborns with CF suggest that this new model will help improve understanding of the disease and may also speed discovery of new treatments. The study is published in the Sept. 26 issue of Science.

CF is a common hereditary disease that affects multiple organ systems, including the intestines, pancreas, and lung. Mice with CF-causing mutations have helped researchers learn more about this disease, however, differences in physiology and biology mean that mice with CF mutations do not develop many of the typical symptoms that affect humans with CF.


Cystic Fibrosis (CF) continues to be a lethal disease for humans despite the identification of the problematic gene two decades ago. Many humans born with CF – the most common genetic disease in Caucasians - often die because of a lung disease developed later. Scientists have been unable to develop an animal model that develops the fatal lung disease. Now, a University of Missouri researcher is producing pigs born with cystic fibrosis that mimic the exact symptoms of a newborn with CF. The researchers are hopeful that these pigs will continue to mimic the human symptoms so the fatal lung disease can be studied and ultimately treated.

"Right now, if you want to do experiments to find treatments or therapies for the lung disease that is fatal for people with CF, you would have to experiment on kids that have CF," said Randy Prather, distinguished professor of reproductive biotechnology in the MU College of Agriculture, Food and Natural Resources.

"When the genetic mutation is introduced into mice, they do not display the symptoms of CF. That's why these new swine models are so important. We have been able to get them through the initial stages of the disease, which they display just like humans, and now we are just waiting for them to grow and potentially develop the lung disease so we can start experimenting in ways that have never been possible."

Prather collaborated with Michael Welsh from the Howard Hughes Medical Institute at the University of Iowa. To create the genetic defect in pigs, a team led by Welsh made genetic modifications in pig cells. Prather's group then generated the genetically modified pigs from the cells using a process known as nuclear transfer. The pigs – called founder animals - that were produced carried only one copy of the mutated gene. Prather bred the pigs naturally and now many piglets have been born with CF.

Once a litter is born, the piglets are immediately flown to Iowa where physicians who perform the corrective surgery on human newborns with CF do the same for the pigs. Meanwhile, MU researchers perform analysis during the transit to determine which piglets have the mutations

"So far, all the mutations in the pigs have exactly mimicked the problems in humans born with CF," Prather said.

"The whole cellular physiology of the pig is similar to humans. That's why having this break- through model is so exciting for the potential it has to move research on cystic fibrosis forward."

"Lack of a better model has hampered our ability to answer long-standing questions in CF," explained Christopher Rogers, Ph.D., a former postdoctoral fellow in internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine, and one of the study's lead authors.

"The CF pig provides a unique opportunity to study one of the most common genetic diseases, and we hope to translate this new knowledge into better therapies and preventions."

In addition to Rogers, co-lead authors of the study were David Stoltz, M.D., Ph.D., UI assistant professor of internal medicine, and David Meyerholz, D.V.M., Ph.D., UI assistant professor of pathology.

The senior study author was Michael Welsh, M.D., UI professor of internal medicine and molecular physiology and biophysics, who holds the Roy J. Carver Chair of Internal Medicine and Physiology and Biophysics. Welsh also is a Howard Hughes Medical Institute investigator.

CF occurs when a person inherits two mutated copies of the CFTR gene leading to loss of ion channel function that adversely affects many organs. To create the CF pigs, the researchers used gene targeting to disrupt one copy of the normal gene in pig cells. They then cloned these altered cells to produce pigs with only one good copy of the gene. Like human CF-carriers, these animals did not show disease symptoms. The pigs were then bred naturally, and about one in four of the piglets were born with two disrupted copies of the gene.

The researchers established that piglets lacking CFTR have the abnormal ion channel activity that is a hallmark of CF disease. They also showed that the CF piglets develop the same disease characteristics that are commonly seen in newborn humans with CF, including a bowel obstruction known as meconium ileus, which often is the first sign of CF in humans. The pigs also have an abnormal pancreas, liver, and gall bladder, similar to CF patients.

"Thus far, the clinical, physiological and age-related appearance of disease in the pigs, as well as the organs involved, mimic CF seen in people," Stoltz said.

A primary cause of death and disability in patients with CF is lung disease. However, many questions remain about how infection and inflammation leads to lung damage. In the study, the lungs of the newborn CF pigs appeared similar to the lungs of their normal littermates and had no sign of infection or inflammation, possibly shedding some initial insight on the process. As the CF pigs mature and are exposed to airborne bacteria and viruses, the researchers hope to learn more about how and why lung disease develops in patients with CF.

"Researchers can now begin to study the disease progression as it is happening, something not possible in humans," Meyerholz said.

Reference:
Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs
Christopher S. Rogers, David A. Stoltz, David K. Meyerholz, Lynda S. Ostedgaard, Tatiana Rokhlina, Peter J. Taft, Mark P. Rogan, Alejandro A. Pezzulo, Philip H. Karp, Omar A. Itani, Amanda C. Kabel, Christine L. Wohlford-Lenane, Greg J. Davis, Robert A. Hanfland, Tony L. Smith, Melissa Samuel, David Wax, Clifton N. Murphy, August Rieke, Kristin Whitworth, Aliye Uc, Timothy D. Starner, Kim A. Brogden, Joel Shilyansky, Paul B. McCray, Jr., Joseph Zabner, Randall S. Prather, Michael J. Welsh
Science 26 September 2008, Vol. 321. no. 5897, pp. 1837 – 1841, DOI: 10.1126/science.1163600

New Pig Model Could Improve Understanding of Cystic Fibrosis
HHMI NEWS - September 26, 2008
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What to Do With Leftover Embryos in the US?

What to Do With Leftover Embryos in the US?
Thursday, 25 September 2008

The majority of infertility patients are in favour of using leftover embryos for stem cell research and would also support selling leftover embryos to other couples, according to a recent survey.

The survey is published in two related studies in the September issue of the journal Fertility and Sterility.

The researchers surveyed 1,350 women who presented for infertility at a large, university hospital-based fertility centre in Illinois. The survey included 24 questions on patient demographics, obstetric and infertility history, and opinions about using extra embryos for stem cell research and selling extra embryos to other couples.

Assisted reproductive technology has resulted in the creation and cryopreservation of extra embryos at fertility centres across the country. It was estimated in 2002 that 396,526 embryos were in storage at US fertility clinics, according to previously published research.

These embryos may be used for future pregnancy attempts, donated to other couples or agencies, given to researchers, or discarded.

Because infertility patients are the gatekeepers of these leftover embryos, it is important to understand their opinions, according to Dr. Tarun Jain, University of Illinois at Chicago assistant professor of reproductive endocrinology and infertility, clinical IVF director, and lead author of the study.

When asked if using leftover embryos for stem cell research should be allowed, 73 percent of the 636 respondents who stated a definitive opinion answered yes.

"Infertility patients, in general, are altruistic, and it makes sense that they would try to advance medicine and help others," said Jain.

African Americans and Hispanics were less likely to approve of using leftover embryos for stem cell research, compared with Caucasians. Patients younger than 30, Protestant, less wealthy and single were also less likely to support using leftover embryos for stem cell research.

The researchers also asked infertility patients if they would be willing to sell their extra embryos to other couples, a practice that is considered ethically unacceptable by the American Society for Reproductive Medicine and the American College of Obstetricians and Gynecologists.

There is an emerging demand from infertility patients who cannot conceive using their own oocytes, or eggs, to purchase leftover, pre-existing embryos because it is a more cost-effective option than using an egg donor, according to the authors.

When asked if selling leftover embryos to other couples should be allowed, 56 percent of the 588 respondents who stated a definitive opinion answered yes.

Hispanics were less likely to approve of selling extra embryos when compared with Caucasians, but all East Indian respondents approved of the practice. Women who had never been pregnant were also less likely to approve, according to the study.

The authors say this is the first survey to examine the opinions of a general infertility population related to the use of leftover embryos and to analyze the results based on the patients' socio-demographic and reproductive backgrounds.

"Given the potential for a significant increase in the commoditizing of spare embryos, medical societies and policy makers may need to pay close attention to this controversial area," conclude Jain and co-author Stacey Missmer from Brigham and Women's Hospital and Harvard Medical School.
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Well Protected Olympics!

Well Protected Olympics!

Outside the Olympic tennis court.
© CellNEWS All rights reserved.

ZenMaster

Breakthrough in Spinal Injury Treatment

Breakthrough in Spinal Injury Treatment
Friday, 19 September 2008

Researchers in Rochester, N.Y., and Colorado have shown that manipulating stem cells prior to transplantation may hold the key to overcoming a critical obstacle to using stem cell technology to repair spinal cord injuries.

Research from a team of scientists from the University of Rochester Medical Center and the University of Colorado Denver School of Medicine, published today in the online Journal of Biology, may lead to improved spinal cord repair methods that pave the way for victims of paralysis to recover the use of their bodies without the risk of transplant-induced pain syndromes.

The research focuses on a major support cell in the central nervous system called astrocytes. When nerve fibres are injured in the spinal cord, the severed ends of the nerve fibres fail to regenerate and reconnect with the nervous system circuitry beyond the site of the injury. During early development, astrocytes are highly supportive of nerve fibre growth, and scientists believe that if properly directed, these cells could play a key role in regenerating damaged nerves in the spinal cord.

The Rochester team – which consists of biomedical geneticists Chris Proschel, Ph.D., Margot Mayer-Proschel, Ph.D., and Mark Noble, Ph.D. – are pioneers in manipulating stem cells to generate nervous system cells that can be used for therapeutic treatments. Rather than transplanting naïve stem cells, the team has adopted an approach of pre-differentiating stem cells into better defined populations of brain cells. These are then selected for their ability to promote recovery. Here glial restricted precursor (GRP) cells – a population of stem cells that can give rise to several different types of brain cell – were induced to make two different astrocyte sub-types using different growth factors that promote cell formation during normal development. Although these astrocytes are made from the same stem cell population, they apparently have very distinct characteristics and functions

"These studies are particularly exciting in addressing two of the most significant challenges to the field of stem cell medicine – defining the optimal cell for repair and identifying means by which inadequately characterized stem cell approaches may actually cause harm," said Noble, who is also co-director of the New State Center of Research Excellence in Spinal Cord Injury, one of the primary funders of the research.

The research team in Colorado, which consisted of Stephen Davies, Ph.D. and Jeannette Davies, Ph.D., transplanted the two types of astrocytes into the injured spinal cords of rats and found dramatically different outcomes. One type of astrocyte was remarkably effective at promoting nerve regeneration and functional recovery, with transplanted animals showing very high levels of new cell growth and survival, as well as recovery of limb function. However, the other type of astrocyte not only failed to promote nerve fibre regeneration or functional recovery but also caused neuropathic pain, a severe side effect that was not seen in rats treated with the beneficial astrocytes. Moreover, transplantation of the precursor cells themselves, without first turning them into astrocytes, also caused pain syndromes without promoting regeneration.

Using signal molecules known to be involved in the generation of embryonic astrocytes during spinal cord development, the researchers were able to make pure cultures of two different types of astrocytes from the glial restricted precursor (GRP) cells.

When the research team in Colorado, transplanted these two types of astrocytes into the injured spinal cord, they had dramatically different effects. One type of astrocyte called GDAsBMP was remarkably effective at promoting nerve regeneration and recovery of limb motion when transplanted into spinal cord injuries. However, the other type of astrocyte cell generated called GDAsCNTF, not only failed to promote nerve fibre regeneration or functional recovery but also caused neuropathic pain, a severe side effect that was not seen in rats treated with GDAsBMP.

"To our knowledge, this is the first time that two distinct sub-types of astrocytic support cells generated from a common stem cell-like precursor have been shown to have robustly different effects when transplanted into the injured adult nervous system," said Mayer-Proschel.

Transplantation of the stem cell-like precursor cells without first turning them into astrocytes, also caused pain syndromes and no spinal repair, Davies said.

"It has long been a concern that therapies that promote growth of nerve fibres in the injured spinal cord would also cause sprouting in pain circuits," said Stephen Davies.

"However by using the right astrocytes to repair spinal cord injuries we can have all the gains without the pain, while these other cell types appear to provide the opposite – pain but no gain."

"These results emphasize the importance of astrocytes in controlling the outcome of neurological disease processes," said Proschel.

"In addition, because transplants of undifferentiated stem cells harbour the risk of making deleterious astrocytes, it is important to understand their properties and how they might form. By being able to study different types of astrocytes derived from a common neural precursor, we are now underway to finding means of preventing the formation of the deleterious astrocyte type in the first place."

The research teams considered the distinction between the effects of GDAsBMP, GDAsCNTF and GRP cells a "breakthrough" that might change the way stem cell technologies are used to repair spinal cord injuries.

Controlling the development of stem cells immediately before transplanting them into injured spinal cords is essential because doctors cannot rely on the injured tissues of the body to create the right types of cells from "naïve" stem cells.

Co-author Mark Noble said:

"These studies are particularly exciting in addressing two of the most significant challenges to the field of stem cell medicine – defining the optimal cell for tissue repair and identifying means by which inadequately characterized approaches may actually cause harm.' To that end, the researchers are developing a safe, efficient and cost-effective way to make human GDAsBMP with an eye toward testing this new stem cell technology in humans.”

The research teams in Denver and Rochester consider the dramatically dissimilar outcomes between the different astrocyte transplants a development that can change the way stem cell technologies are used to repair spinal cord injuries. To that end, the researchers are in the process of developing a safe, efficient and cost-effective way to use this approach to better define the optimal human astrocytes with an eye toward use for clinical trials.

Refeerence:
Transplanted astrocytes derived from BMP- or CNTF-treated glialrestricted precursors have opposite effects on recovery and allodynia after spinal cord injury
Jeannette E Davies, Christoph Proschel, Ningzhe Zhang, Mark Noble, Margot Mayer-Proschel and Stephen JA Davies
Journal of Biology 2008, 7:24, doi:10.1186/jbiol85
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Different Stem Cell Types Defined by Exclusive Combinations of Genes Working Together

Singapore scientists report findings in Cell Stem Cell
Thursday, 18 September 2008

In the new issue of Cell Stem Cell, scientists report that the same transcription factor, which is crucial for the survival of different stem cell types, can behave differently.

This study clearly showed for the first time that exclusive combinations of genes working together define different types of stem cells, and this is under the influence of a single key stem cell factor (called Sall4).

The finding is timely since other researchers have recently revealed that specific genetic recipes can be used to turn non-stem cells into different stem cells that can be useful clinically.

This finding reveals important insights about how scientists may be able to manipulate and engineer different stem cells for the treatment of human degenerative disorders.

Understanding the behaviour of transcription factors, a class of gene regulators, helps pave the way for important advancements in stem cell technology and clinical research.

Stem cells are important for the cell-based therapy of many degenerative tissue disorders. Each type of body tissue has its own unique type of stem cells whose behaviour is controlled by different sets of genes.

Given the enormous complexity of each stem cell type and the underlying genetic bases for their unique purpose, it has been a major challenge for scientists to unravel the similarities and differences between the different stem cells.

The latest research, led by Bing Lim, Senior Group Leader at the Genome Institute of Singapore (GIS), focused on identifying and understanding the functions of powerful genetic molecules, also known as "stem cell factors".

Dr. Bing Lim said:

"This new discovery has provided us with important new leads and ideas on how to grow and expand various stem cells for clinical research and treatment needs."

Dr. Daniel Tenen, Professor of Medicine at Harvard Medical School, and Director for Cancer Research Centre of Excellence at the National University of Singapore, said:

"These studies are of great significance, as they provide important clues as to how a single transcription factor might regulate different targets in different stem cells."

Interestingly, this stem cell factor also appeared to be associated with certain diseases, particularly leukaemia.

Dr. Li Chai, Instructor at the Department of Pathology at the Harvard Medical School, added that, "as Sall4 plays an important role in both normal hematopoietic stem cell function and in leukaemia stem cells, these findings may have clinical relevance; they may lead to understanding differences between normal and cancer stem cells."

Genome Institute of Singapore (GIS):
GIS is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Agency for Science, Technology and Research:
The Agency for Science, Technology and Research, or A*STAR, is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.

Reference:
Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages.
Chin Yan Lim, Wai-Leong Tam, Jinqiu Zhang, Haw Siang Ang, Hui Jia, Leonard Lipovich, Huck-Hui Ng, Chia-Lin Wei, Wing Kin Sung, Paul Robson, Henry Yang and Bing Lim
Cell Stem Cell, 10.1016/j.stem.2008.08.004
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RNA Interference Plays Bigger Role Than Previously Thought

IBM and Genome Institute of Singapore report in Nature
Thursday, 18 September 2008

In a paper published online in the journal Nature, IBM and the Genome Institute of Singapore (GIS) reported findings from a joint research study that provides new information on how stem cell differentiation is controlled by microRNAs.

The two teams have shown that microRNAs — small molecules that are an important regulatory component in the machinery of living cells — have roles that go well beyond what was previously thought.

In 2006, IBM scientists developed a mathematical model that led to a conjecture about an expanded role for microRNAs. The team decided to test the hypothesis by focusing on mouse stem cells. IBM used computation to guide the experimental effort that GIS carried out.

The work is expected to provide new insights on stem cell differentiation as well as on the role of microRNAs in cell process regulation and the onset of cancer, neurodegenerative disorders, diabetes and other diseases. The research is also expected to suggest future avenues for novel diagnostics and the development of therapeutics.

"We have made yet another step towards understanding the intricate nature of microRNAs and the roles they play in the regulation of cellular processes," said Isidore Rigoutsos, manager of the Bioinformatics Group in IBM Research's Computational Biology Center.

"The finding that microRNAs can extensively target locations in the amino acid coding regions of a transcript is an exciting discovery and reveals another important aspect of microRNA activity."

GIS Senior Group Leader Bing Lim added:

"We learn from this study that the targeting of coding regions by microRNAs can also have a real impact on cells. We observed that a single microRNA forced into the powerful embryonic stem cell can impose differentiation. This is exciting because one could envisage using microRNAs as a small molecule to control the differentiation of stem cells, or to make new stem cells. The fun part of this research was the visualization of a trend of thought from computational prediction all the way to cell transformation."

Details of discovery:
For more than a decade, microRNAs were assumed to interact primarily with their targets through the 3' un-translated region (3'UTR) of the targets' mRNA. The nucleotide sequences of the targeted locations were believed to be generally conserved across different organisms whereas interactions with mRNA regions beyond the 3'UTR were thought to be atypical.

Some of the new research findings suggest that microRNA targets in the amino acid coding region (CDS) of a gene's mRNA may in fact be as frequent as those in the mRNA's 3'UTR, providing experimental evidence to a conjecture put forth in an earlier publication by the two teams. It also shows that a gene's CDS serves as template of microRNA targeting activity, in addition to its coding for the corresponding protein's amino acid sequence.

Working with three microRNAs whose expression increases upon differentiation of mouse embryonic stem cells (ESCs), the teams showed that Nanog, Oct4 and Sox2, three transcription factors that are central to maintaining the pluripotency of mouse ESCs and determining the initiation of differentiation, are controlled through their CDS region by the three studied microRNAs. By introducing mutations at the identified target locations, the two teams showed that they could prevent the down-regulation of these transcription factors and delay stem cell differentiation.

For the majority of the validated microRNA targets, their sequence is not conserved in the rhesus monkey and mouse counterparts of Nanog, Oct4 and Sox2. This suggests that seeking putative microRNA targets by aligning the instances of a gene across different organisms will underestimate the number of bona fide microRNA targets.

Additionally, the studied microRNAs generally have multiple targets in the CDS region of the same gene possibly suggesting an underlying need for redundancy that can ensure the down-regulation of the intended target.

Finally, several of the studied targets stride exon-exon junctions: this finding suggests that microRNAs play a role in the selective targeting of a gene's splice variants.

"This discovery has vast implications for the role that computational models can play in biological science," said Ajay Royyuru, senior manager for the Computational Biology Center at IBM Research.

"Computational biology allows scientists to develop theories using powerful computers and even preliminarily prove those theories prior to conducting experiments in wet labs – which reduce the time spent on trial and error throughout the process of scientific discovery."

GIS Executive Director Edison Liu said:

"This work is a great example of how future medical discovery will progressively require the joint efforts of computer scientists working in conjunction with biologists. The complexity of the control of human cells through regulatory networks demands computational modelling in order to decipher the signals from the noise. But in the end, it still boils down to doing the lab experiment."

About IBM Research:
IBM Research is the world's largest information technology research organization, with about 3,000 scientists and engineers globally.

About Genome Institute of Singapore (GIS):
GIS, a member of the Agency for Science, Technology and Research (A*STAR), is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS pursues the integration of technology, genetics and biology towards the goal of individualized medicine. Key research areas include systems biology, stem cell & developmental biology, cancer biology & pharmacology, human genetics, infectious diseases, genomic technologies, and computational & mathematical biology. GIS' genomics infrastructure is utilized to train new scientific talent, function as a bridge for academic and industrial research and explore scientific questions of high impact.

Reference:
miRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation
Yvonne Tay, Jinqiu Zhang, Andrew M. Thomson, Bing Lim & Isidore Rigoutsos
Nature, 17 September 2008, doi:10.1038/nature07299
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Human Skin Cells Turned Into Insulin-producing Cells

Human Skin Cells Turned Into Insulin-producing Cells
Thursday, 18 September 2008

Researchers at the University of North Carolina at Chapel Hill School of Medicine have transformed cells from human skin into cells that produce insulin, the hormone used to treat diabetes.

The breakthrough may one day lead to new treatments or even a cure for the millions of people affected by the disease, researchers say.

The approach involves reprogramming skin cells into pluripotent stem cells, or cells that can give rise to any other foetal or adult cell type, and then inducing them to differentiate, or transform, into cells that perform a particular function – in this case, secreting insulin.

Several recent studies have shown that cells can be returned to pluripotent state using "defined factors" (specific proteins that control which genes are active in a cell), a technique pioneered by Dr. Shinya Yamanaka, a professor at Kyoto University in Japan.

However, the UNC study is the first to demonstrate that cells reprogrammed in this way can be coaxed to differentiate into insulin-secreting cells. Results of the study are published online in the Journal of Biological Chemistry.

"Not only have we shown that we can reprogram skin cells, but we have also demonstrated that these reprogrammed cells can be differentiated into insulin-producing cells which hold great therapeutic potential for diabetes," said study lead author Yi Zhang, Ph.D., Howard Hughes Medical Institute investigator, professor of biochemistry and biophysics at UNC and member of the Lineberger Comprehensive Cancer Center.

"Of course, there are many years of additional studies that are required first, but this study provides hope for a cure for all patients with diabetes," said John Buse, M.D., Ph.D., president of the American Diabetes Association and professor and chief of the endocrinology division in the UNC School of Medicine's department of medicine.

About 24 million Americans suffer from diabetes, a disease that occurs when the body is unable to produce or use insulin properly. Virtually all patients with type I diabetes, the more severe of the two types, must rely on daily injections of insulin to maintain their blood sugar levels.

Recent research exploring a possible long-term treatment – the transplantation of insulin-producing beta cells into patients – has yielded promising results. However, this approach faces its own challenges, given the extreme shortage of matched organ donors and the need to suppress patients' immune systems.

The work by Zhang and other researchers could potentially address those problems, since insulin-producing cells could be made from diabetic patients' own reprogrammed cells.

Zhang is collaborating with Buse to obtain skin samples from diabetes patients. He said he hoped his current experiments will take this approach one step closer to a new treatment or even a cure for diabetes.

Reference:
Generation of insulin-secreting islet-like clusters from human skin fibroblasts
Keisuke Tateishi, Jin He, Olena Taranova, Gaoyang Liang, Ana C. D'Alessio, and Yi Zhang
J. Biol. Chem, 10.1074/jbc.M806597200
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Scientists Identify Genes Capable of Regulating Stem Cell Function

Animal model provides insight on pathways used for adult tissue maintenance and regeneration
Wednesday, 17 September 2008

Scientists from The Forsyth Institute, Boston, MA, and the Howard Hughes Medical Institute at the University of Utah School of Medicine have developed a new system in which to study known mammalian adult stem cell disorders. This research, conducted with the flatworm planaria, highlights the genetic similarity between these invertebrates and mammals in the mechanisms by which stem cell regulatory pathways are used during adult tissue maintenance and regeneration. It is expected that this work may help scientists pursue pharmacological, genetic, and physiological approaches to develop potential therapeutic targets that could repair or prevent abnormal stem cell growth that can lead to cancer.

In recent years, planarians have been recognized as a powerful model system in which to molecularly dissect conserved stem cell regulatory mechanisms in vivo. This research reveals that planaria are also a great model in which to study the molecular relationship between stem cells and cancer. The gene characterized in this study (PTEN) is one of the most commonly mutated genes in human cancers. As in human beings, genetic disturbance of the gene in planarians led to miss-regulation of cell proliferation resulting in cancer-like characteristics. These results indicate that some of the pattern control mechanisms that enable regeneration of complex structures may go awry in cancer.

Abnormal stem cell proliferation in planarians is induced by genetic manipulation of conserved cellular signalling pathways. These abnormal cells can be specifically targeted without disturbing normal stem cell functions that support adult tissue homeostasis and regeneration. Importantly, this type of analysis could not be achieved in more traditional adult invertebrate model systems such as the fruit fly Drosophila and the nematode C. elegans. This research was published in the journal Disease Models & Mechanisms online on August 30.

According to the paper's lead author, Dr. Néstor J. Oviedo, an Assistant Research Investigator in the Forsyth Center for Regenerative and Developmental Biology, this work provides new opportunities to expand knowledge of this regulatory molecule and the role it plays in cancer and tissue regeneration.

"Our findings demonstrate that important signalling pathways regulating adult stem cell proliferation, migration and differentiation are evolutionarily and functionally conserved between planarians and mammals. Planarians are poised to not only advance the understanding of how diverse adult tissues are functionally maintained in vivo, but also will enhance our capabilities to identify, prevent, and remediate abnormal stem cell proliferation."

Summary of Study
The scientists have identified two genes, Smed-PTEN-1 and Smed-PTEN-2, capable of regulating stem cell function in the planarian Schmidtea mediterranea. Both genes encode proteins homologous to the mammalian tumour suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Inactivation of Smed-PTEN-1and -2 by RNA interference (RNAi) in planarians disrupts regeneration, and leads to abnormal outgrowths in both cut and uncut animals followed soon after by death (lysis). The resulting phenotype is characterized by hyperproliferation of neoblasts (planarian stem cells), tissue disorganization and a significant accumulation of post-mitotic cells with impaired differentiation capacity. Further analyses revealed that rapamycin selectively prevented such accumulation without affecting the normal neoblast proliferation associated with physiological turnover and regeneration. In animals in which PTEN function is abrogated, the HHMI/University of Utah and Forsyth researchers also detected a significant increase in the number of cells expressing the planarian Akt gene homolog (Smed-Akt). However, functional abrogation of Smed-Akt in Smed-PTENRNAi-treated animals does not prevent cell overproliferation and lethality, indicating that functional abrogation of Smed-PTEN is sufficient to induce abnormal outgrowths. Altogether, the data reveal roles for PTEN in the regulation of planarian stem cells that are strikingly conserved to mammalian models. In addition, the results implicate this protein in the control of stem cell maintenance during the regeneration of complex structures in planarians.

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The planarian Schmidtea mediterranea. Credit: A. Sánchez Alvarado.

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The PTEN molecules were originally identified and characterized in the laboratory of Dr. Alejandro Sanchez Alvarado, HHMI investigator and Professor of Neurobiology and Anatomy at the University of Utah School of Medicine. Dr. Sánchez Alvarado's is the paper's senior author. His laboratory is engaged in the identification of the molecular and cellular basis of animal regeneration. His laboratory's work on planarians has led to the establishment of this organism as an important model system to study stem cells, regeneration and tissue homeostasis.

The Forsyth research team is led by Michael Levin, Ph.D., Senior Member of the Staff in The Forsyth Institute and the Director of the Forsyth Center for Regenerative and Developmental Biology. Through experimental approaches and mathematical modelling, Dr. Levin and his group examine the processes governing large-scale pattern formation and biological information storage during animal embryogenesis. The lab investigates mechanisms of signalling between cells and tissues that allow a living system to reliably generate and maintain a complex morphology. The Levin team studies these processes in the context of embryonic development and regeneration, with a particular focus on the biophysics of cell behaviour.
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Embryonic Stem Cells Reduce Transplantation Rejection

Embryonic Stem Cells Reduce Transplantation Rejection
Monday, 15 September 2008

Researchers have shown that immune-defence cells influenced by embryonic stem cell-derived cells can help prevent the rejection of hearts transplanted into mice, all without the use of immunosuppressive drugs.

The University of Iowa and the Iowa City Veterans Affairs (VA) Medical Center finding has implications for possible improvements in organ and bone marrow transplantation for humans. The study results appeared Friday in the online journal PLoS ONE, published by the Public Library of Science.

People who need bone marrow or solid organ transplantation must take immunosuppressive drugs that can cause side effects nearly as severe as the disease they have. They also can experience graft-versus-host disease, which can cause death.

These problems are spurring researchers to develop methods to reduce transplantation rejection, said the study's principal investigator Nicholas Zavazava, M.D., Ph.D., professor of internal medicine and director of transplant research at the University of Iowa Carver College of Medicine.

"The idea behind the study is to 'prep' a recipient's immune system to make it receptive to the eventual organ or bone marrow donor's genetic make-up," said Zavazava, who also is a staff physician with the Iowa City VA Medical Center.

"The approach involves taking embryonic stem cells with the same genetic background as the donor from which the organ or bone marrow ultimately will come and adapting them into another type of stem cell that can be injected into the recipient."

Specifically, the team treated mouse embryonic stem cells with a "cocktail" of growth factors, causing them to become blood stem cells. These cells express very low levels of so-called "transplantation antigens" and are therefore protected from immunological rejection.

The researchers then injected the blood stem cells into the recipient mouse's blood circulation. These stem cells found their way into the recipient mouse's thymus, where, as happens in humans, the recipient's own bone marrow cells typically migrate and develop into immune-defence cells known as T-cells.

With the donor-related blood stem cells now present in the thymus, the mouse recipient's own T-cells learned to recognize them as part of itself and therefore caused no rejection. These now 'donor-friendly' T-cells then circulated within the recipient mouse's blood, Zavazava explained.

"When we then transplanted into the recipient mouse a donor mouse heart that had the same genetic make-up as the previously injected stem cells, the T-cells didn't reject the heart because they recognized it as compatible," Zavazava said.

"If we could eventually use this approach for organ transplantation in humans, it would be a huge advantage over the method we're currently using," he added.

In addition to its potential for organ transplantation treatment, the embryonic stem cell-based method might also have implications for treating bone marrow diseases such as leukaemia.

Because a mouse is so small, it was not possible in the study to remove the animal's existing heart and replace it with another. Thus, to test for transplant success, the study approach involved leaving the original heart intact, transplanting a second functional heart into the abdomen and then linking the transplanted heart to the aorta.

The UI study built on previous research led by Zavazava that focused on the concept of using embryonic stem cells as an alternative source of cells for traditional bone marrow transplantations.

The current study was supported by grants from the National Heart, Lung and Blood Institute, a VA Merit Review and the Roche Organ Transplantation Research Foundation.

Reference:
ES-Cell Derived Hematopoietic Cells Induce Transplantation Tolerance
Sabrina Bonde, Kun-Ming Chan, Nicholas Zavazava
PLoS ONE 3(9): e3212. doi:10.1371/journal.pone.0003212
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Embryonic Stem Cells Repair Congenital Heart Defect

Potential therapy for inherited conditions
Friday, 12 September 2008

Mayo Clinic investigators have demonstrated that stem cells can be used to regenerate heart tissue to treat dilated cardiomyopathy, a congenital heart defect. Publication of the discovery was expedited by the editors of Stem Cells and appeared online on the journal's Web site.

The study expands on the use of embryonic stem cells to regenerate tissue and repair damage after heart attacks and demonstrates that stem cells also can repair the inherited causes of heart failure.

"We've shown in this transgenic animal model that embryonic stem cells may offer an option in repairing genetic heart problems," says Satsuki Yamada, M.D., Ph.D., cardiovascular researcher and first author of the study.

"Close evaluation of genetic variations among individuals to identify optimal disease targets and customize stem cells for therapy opens a new era of personalized regenerative medicine," adds Andre Terzic, M.D., Ph.D., Mayo Clinic cardiologist and senior author and principal investigator.

How They Did It
The team reproduced prominent features of human malignant heart failure in a series of genetically altered mice. Specifically, the "knockout" of a critical heart-protective protein known as the K-ATP channel compromised heart contractions and caused ventricular dilation or heart enlargement. The condition, including poor survival, is typical of patients with heritable dilated cardiomyopathy.

Researchers transplanted 200,000 embryonic stem cells into the wall of the left ventricle of the knockout mice. After one month the treatment improved heart performance, synchronized electrical impulses and stopped heart deterioration, ultimately saving the animal's life. Stem cells had grafted into the heart and formed new cardiac tissue. Additionally, the stem cell transplantation restarted cell cycle activity and halved the fibrosis that had been developing after the initial damage. Stem cell therapy also increased stamina and removed fluid build-up in the body, so characteristic in heart failure.

The researchers say their findings show that stem cells can achieve functional repair in non-ischemic (cases other than blood-flow blockages) genetic cardiomyopathy. Further testing is underway.

Reference:
Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy
Satsuki Yamada, Timothy J. Nelson, Ruben Crespo, Carmen Terzic, Xiao Ke Liu, Takashi Miki, Susumu Seino, Atta Behfar, Andre Terzic
Stem Cells, published online July 31, 2008
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Keeping Nerve Axons on Target

A second career for a growth factor receptor
Friday, 12 September 2008

Neurons constituting the optic nerve wire up to the brain in a highly dynamic way. Cell bodies in the developing retina sprout processes, called axons, which extend toward visual centres in the brain. They are lured by attractive cues and making U-turns when they take the wrong path. How they find targets so accurately is a central question of neuroscience today.

Using the mouse visual system, a team of Salk Institute for Biological Studies investigators led by Dennis O'Leary, Ph.D., identified an unanticipated factor that helps keep retinal axons from going astray. They report in the Sept. 11 issue of Neuron that p75, a protein previously known to regulate whether neurons live or die, leads a double life as an axon guidance protein.

"Historically, we thought that factors that mediate cell survival and those controlling axon guidance were part of two separate processes," says O'Leary, a professor in the Molecular Neurobiology Laboratory.

"But in this study we show a direct interaction between these two systems."

Collaborating with Kuo-Fen Lee, Ph.D., professor in the Clayton Foundation Laboratories for Peptide Biology, the O'Leary team observed a defect in mice genetically engineered to lack p75. Through their synaptic connections, retinal axons develop a two-dimensional map of the retina in their targets in the brain. In the mice lacking p75, retinal axons stopped short of their final target and formed a map that was shifted forward to the superior colliculus, a major visual centre in the brain.

Such a defect in p75-null mice was puzzling: researchers have studied p75 for decades and found it associated with activities as varied as neuronal growth, survival, and degeneration. Axonal migration was not among them.

Todd McLaughlin, Ph.D., a senior research associate in the lab and co-first author, says that insight came in an eureka moment:

"We realized that what we were observing in these mice was similar to what would happen if you deleted a gene called ephrin-A from the retina."

Unlike p75, ephrin-A was a well-characterized sender and receiver of axon guidance signals, but it lacked appendages normally seen on proteins controlling axon migration. p75, however, displayed those elements, suggesting that the proteins could pair up — one receiving the migration signal and the other transmitting it.

The research team then turned to biochemical analyses and with the added expertise of Tsung Song, a research associate in Dr. Lee's lab, obtained evidence that supported this hypothesis. The group found that ephrin-A and p75 complexes in axonal membranes and showed that when activated they could generate the signals required to guide axons and develop their map in the brain.

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When immature neurons are placed on a microscopic running track, where flanking lanes are carpeted with repellent factors, their growing axons remain in their lanes (top). Neurons from mice lacking p75 are unreceptive to repulsive cues: when placed on the track, their axons meander all over the field, crossing lanes and running down repellent-covered stripes (bottom). Credit: Courtesy of Dr. Yoo-Shick Lim, Salk Institute for Biological Studies.

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But the clincher was the "stripe assay," a classical screen for guidance molecules that repel growing axons. In it, an immature neuron is placed on a microscopic running track, just as it starts to develop an axon. When flanking lanes are carpeted with repellent factors, the sprouting axon bursts from the block but remains in its lane like a well-coached runner, avoiding neighbouring tracks.

Constructing tracks made from the repulsive factor sensed by ephrin-A, the researchers confirmed that axons from normal retinal neurons stayed in their lanes when flanked by the repellent. But neurons from mice lacking p75 were unreceptive to repulsive cues: when placed on the track their axons meandered all over the field, crossing lanes and running down repellent-covered stripes.

Why retinal neurons missed the target in the p75-minus mice became clear: they lacked the cellular machinery to respond to critical repellent signals encountered in the brain and stopped migrating prematurely.

Among its myriad functions, p75's new role is a critical one.

"Repulsion is probably the dominant force in axon guidance and a stronger influence than attraction," explains McLaughlin, noting that providing axons with a lot of options is not the way to build a brain.

"Attraction is like finding the best seat in an empty movie theatre, but repulsion is like picking the lone empty seat in a full theatre."

"We have shown that ephrin-A cannot transduce an intracellular signal by itself and instead requires the co-receptor p75," summarizes Yoo-Shick Lim, Ph.D., a postdoctoral fellow in the O'Leary lab and co-first author.

"This interaction could operate in numerous events in neural development."

O'Leary believes that identifying mechanisms underlying developmental events is fundamental to understanding the basis of any biological disorder.

"These studies establish that two distinct molecular systems, neurotrophins and axon guidance, both critical for neural development directly collaborate to develop neural connectivity”.

“Findings such as these lend critical insight into how one might repair damage to the nervous system due to genetic defects, tumours or wounds to the brain or spinal cord," he says.

"We hope one day to be able to repair these defects and get cells to form functional connections again."

About The Salk Institute:
The Salk Institute for Biological Studies in La Jolla, California, is an independent non-profit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, MD, whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

Reference:
p75NTR Mediates Ephrin-A Reverse Signaling Required for Axon Repulsion and Mapping
Yoo-Shick Lim, Todd McLaughlin, Tsung-Chang Sung, Alicia Santiago, Kuo-Fen Lee, and Dennis D.M. O'Leary
Neuron, Vol 59, 746-758, 11 September 2008
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Ban Cluster Bombs Now!

Ban Cluster Bombs Now!
Friday, 12 September 2008

Help Ban Cluster Bombs Now!

The Cluster Munition Coalition, in collaboration with Mines Action Canada, re-launched the People’s Treaty on 30 May – the final day of the Dublin Diplomatic Conference on Cluster Munitions after the 107 participating states unanimously adopted the new treaty. Following this, the campaign is now working to ensure that as many states as possible sign the new treaty in Oslo from 2-3 December 2008.
Go to:
http://www.minesactioncanada.org/peoples_treaty/index.html and sign up!

See more about cluster bombs here:
http://banclusterbombs.smnr.us/
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China Produce Its First IVF Monkeys

Plan to engineer gene-modified monkeys later
Thursday, 11 September 2008

Chinese scientists have created the country's first test-tube monkeys, which are said to be the first step to engineer gene-modified monkeys.

"Our next step is to bring about more test-tube monkeys and eventually make gene-modified monkeys benefiting for medical research," said Dr. Sun Qiang, at the Shanghai Institute of Brain Functional Genomics (IBFG), East China Normal University in Shanghai.

Sun's team capitalized on a few new technologies on stimulating more eggs from female monkeys and collecting semen and mammalian oocytes, as well as new ways of in vitro fertilization and embryo transplantation.

The new technologies "can significantly improve the pregnancy rate and live birth of healthy baby monkeys," the scientist said.

All seven new born monkeys are healthy, Sun said, with the oldest Lele, or Happiness, being aged at one and half years.

Reference:
Efficient reproduction of cynomolgus monkey using pronuclear embryo transfer technique
Qiang Sun, Juan Dong, Wenting Yang, Yujuan Jin, Mingying Yang, Yan Wang, Philip L. Wang, Yinghe Hu and Joe Z. Tsien
PNAS September 2, 2008 vol. 105 no. 35 12956-12960
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Fast iPS Cell Method Described

New Method for Creating Inducible Stem Cells is Remarkably Efficient
Wednesday, 10 September 2008

Some of the most challenging obstacles limiting the reprogramming of mature human cells into stem cells may not seem quite as daunting in the near future. Two independent research papers, published by Cell Press in the September 11th issue of the journal Cell Stem Cell, describe new tools that provide invaluable platforms for elucidating the molecular, genetic, and biochemical mechanisms associated with reprogramming. The new findings also offer considerable hope toward making the reprogramming process more therapeutically relevant.

Although scientists have successfully reprogrammed mature human skin cells into induced pluripotent stem (iPS) cells by expressing a few key transcription factors, the conversion has been extremely inefficient.

"Little is known about the mechanisms by which reprogramming occurs, in part because of the low efficiency," says senior study author Dr. Konrad Hochedlinger from the Harvard Stem Cell Institute. In addition, the iPS cells created thus far have been generated with retroviruses and non-inducible lentiviruses, both of which have major limitations that are not compatible with clinical applications.

The Hochedlinger group created a drug-inducible viral system to generate human iPS cells that were molecularly and functionally similar to human embryonic stem cells. This method was unique in that it allowed the researchers to create iPS cells by using the drug doxycycline to control expression of the necessary factors that had been delivered to the cells with viruses.

The researchers then found that when doxycycline was removed and these "primary" iPS cells differentiated to mature cells, another exposure to the drug reactivated the genes required for reprogramming and induced generation of "secondary" iPS cells at a frequency that was far greater that the initial "primary" conversion. The idea of generating these secondary cells was conceived in previous experiments with mice performed in the lab of Dr. Rudolf Jaenisch from the Massachusetts Institute of Technology.

"The secondary system will enable chemical and genetic screening efforts to identify key molecular constituents of reprogramming, as well as important obstacles in this process, and will ultimately lend itself as a powerful tool in the development and optimization methods to produce human iPS cells," explains Dr. Hochedlinger.

In a separate paper, Dr. Jaenisch's group reports on their success in deriving human secondary iPS cells using doxycycline-inducible transgenes.

"The drug-inducible system we describe represents a novel, predictable, and highly reproducible platform to study the kinetics of iPS cell generation," says Dr. Jaenisch.

"Further, the genetic homogeneity of secondary cells makes chemical and genetic screening approaches to enhance reprogramming efficiency or to replace any of the original reprogramming factors feasible."

Both research teams found that generation of secondary human iPS cells required less time than the initial reprogramming. Interestingly, the time required to generate iPS cells varied among the types of skin cells that were used. For instance, human fibroblasts required several weeks, while keratinocytes required only about 10 days.

"The fast kinetics of reprogramming observed for keratinocytes suggests that these cells would be useful for development and optimization of methods to reprogram cells by transient delivery of factors," suggests Dr. Hochedlinger.

The combined results from both research groups represent a major advance toward more efficient strategies for reprogramming differentiated human cells into iPS cells. The methods described here will not only provide critical insight into the reprogramming process, but also, because of the abbreviated time frame, may lead to the generation of cells that will be amenable for therapies, as reprogramming might be achievable without the prohibitive viruses or genetic modifications.

References:
A High-Efficiency System for the Generation and Study of Human Induced Pluripotent Stem Cells
Nimet Maherali, Tim Ahfeldt, Alessandra Rigamonti, Jochen Utikal, Chad Cowan, and Konrad Hochedlinger
Cell Stem Cell, Vol 3, 340-345, 11 September 2008

A Drug-Inducible System for Direct Reprogramming of Human Somatic Cells to Pluripotency
Dirk Hockemeyer, Frank Soldner, Elizabeth G. Cook, Qing Gao, Maisam Mitalipova, and Rudolf Jaenisch
Cell Stem Cell, Vol 3, 346-353, 11 September 2008
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Common Virus to Combat Deadly Lung Cancer

Common Virus to Combat Deadly Lung Cancer
Wednesday, 10 September 2008

Among the 5,000 studies being discussed by 30,000 oncologists at the 2008 meeting of the American Society of Clinical Oncology (ASCO), a great deal of buzz was generated over the discovery that a substantial subset of patients with non-small cell lung cancer (NSCLC) may not benefit from the most commonly prescribed therapies. About 20% of the more than 180,000 NSCLC patients diagnosed every year in the U.S. have mutations in the K-RAS gene. These patients generally respond poorly to standard chemotherapy treatments as well as newer, more targeted therapies called EGFR inhibitors.

Enter REOLYSIN®, an experimental treatment derived from a common virus called the reovirus. REOLYSIN directly kills many types of cancer cells, works synergistically with many approved chemotherapies and radiation, and may also stimulate the immune system to attack and kill cancer cells.

Following FDA review, Oncolytics Biotech Inc. is initiating a Phase 2 clinical trial at the Ohio State University Medical Center using REOLYSIN in combination with paclitaxel and carboplatin for NSCLC patients with K-RAS or EGFR-activated tumours. Patients with these types of mutations generally represent about half of the NSCLC patients diagnosed annually in the U.S.

REOLYSIN preferentially replicates in cancer cells with an activated RAS pathway. Approximately two thirds of all cancers have an activated RAS pathway, including most metastatic disease. A large number of mutations along the RAS pathway, including mutations in EGFR, Her2, or K-RAS, lead to RAS pathway activation. Recent clinical studies in NSCLC with EGFR-based therapies have shown that the patients with mutations or over expression of EGFR, which are commonly found in NSCLC, derive some clinical benefit from these therapies. However, patients with mutant K-RAS do not generally derive benefit from EGFR-based therapies.

“In this era of personalized cancer treatment, we are quite excited about this trial,” said Dr. Miguel Villalona-Calero, Professor Division of Hematology/Oncology and Department of Internal Medicine and Pharmacology at the Ohio State University Comprehensive Cancer Center, and the principal investigator for the trial.

“Although we have had for some time treatments that target EGFR, K-RAS has been an elusive target. REOLYSIN has the potential to target K-RAS activated tumours, possibly enhancing the beneficial effects produced by chemotherapy.”

However, it is not only patients with mutant K-RAS who might benefit from REOLYSIN combination treatment. The U.S. National Cancer Institute (NCI) recently tested reovirus in combination with a wide range of common chemotherapeutic agents against NSCLC, and found that the combination of reovirus with cisplatin, gemcitabine, mitomycin or vinblastine was synergistic against NSCLC cell lines that were sensitive to the compounds. Interestingly, the combination of reovirus and paclitaxel was uniformly synergistic in all six NSCLC cell lines examined, including in those resistant to paclitaxel or reovirus.

“Previous preclinical data indicates that reovirus tends to localize in the lungs, and we have seen clinical responses in metastatic lung lesions with REOLYSIN as a mono-therapy or in combination with paclitaxel and carboplatin,” said Dr. Brad Thompson, President and CEO of Oncolytics.

“Assuming we get the response we’re anticipating, REOLYSIN could be a strong candidate for late-stage clinical trials in this indication.”

Non-small cell lung cancer is the second most common cancer in men and women and is the leading cause of death among cancer patients. More people die of lung cancer than of colon, breast, and prostate cancers combined. During 2008, there will be approximately 215,020 new cases of lung cancer in the U.S., of which 85% to 90% will be non-small cell lung cancer (NSCLC). Only about 15% of those diagnosed with lung cancer are still alive after five years with the disease.

This trial is designed as a single arm, two-stage, open-label, Phase 2 study of REOLYSIN given intravenously with paclitaxel and carboplatin every three weeks. Patients will receive four to six cycles of paclitaxel and carboplatin in conjunction with REOLYSIN, at which time REOLYSIN may be continued as a mono-therapy. It is anticipated that up to 36 patients will be treated in this trial.

Eligible patients include those with metastatic or recurrent NSCLC with K-RAS or EGFR-activated tumours, who have not received chemotherapy treatment for their metastatic or recurrent disease. Patients must have demonstrated mutations in K-RAS or EGFR, or EGFR gene amplification in their tumours (metastatic or primary) in order to qualify for the trial.

The primary objectives of the Phase 2 trial are to determine the objective response rate of REOLYSIN in combination with paclitaxel and carboplatin in patients with metastatic or recurrent NSCLC with K-RAS or EGFR-activated tumours, and to measure survival and progression-free survival at six months. The secondary objectives are to determine the median survival and duration of progression-free survival in patients, and to evaluate the safety and tolerability of REOLYSIN in combination with paclitaxel and carboplatin in this patient population.
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hESCs Minimized Tissue Injury in Pigs

Lab studies, conducted by Singapore and the Netherlands scientists, show that stem cell secretions minimized tissue injury after heart attack.
Wednesday, 10 September 2008

A novel way to improve survival and recovery rate after a heart attack was reported in the journal Stem Cell Research by scientists at Singapore's Institute of Medical Biology (IMB) and Bioprocessing Technology Institute (BTI) and The Netherlands' University Medical Center Utrecht.

This method, developed in laboratory research with pigs, is the first non-cell based therapeutic application of human embryonic stem cells (hESCs). It entails using secretions from stem cells.

In their studies with pigs, the researchers found that the administration of secretion from stem cells minimized heart injury by enhancing reperfusion therapy (angioplasty and cardiac bypass surgery) and reducing tissue death by another 60%.

Heart function was also markedly improved, the scientists report in the paper, published in the June 2008 issue of the journal.

By demonstrating the efficacy of this secretion in an experimental pig model, currently the best approximation to a human heart attack patient undergoing reperfusion therapy, the researchers say that they have addressed the longstanding problem of reperfusion injury in the most clinically relevant experimental setting.

"Using secretion instead of cells allows us to circumvent many highly intractable problems such as tumour formation, immune compatibility, cell viability, delivery, costs and timeliness," said IMB'S Dr Sai-Kiang Lim, who leads the Singapore-The Netherlands collaboration.

Unlike the more common approach of directly administering stem cells for therapy, this new method carries negligible risk of tumour formation or rejection by the body.

In the pig research model, this approach minimised heart injury after a heart attack, a particularly important consideration since the heart has a limited ability to regenerate.

The research was carried out on pigs because it is the closest animal approximation to the human heart in terms of size, structure and function.

The findings are especially important as they show that the new method can overcome the unwanted side effects of reperfusion, currently the best therapeutic option available to heart attack patients. Reperfusion is the restoration of blood flow to the oxygen-deprived heart after a heart attack.

"This is a major discovery of clinical significance. There are some problems and issues associated with the use of stem cells to treat heart attacks and blocked arteries in the heart, and with this new method, many of these issues are removed. Potentially, we may have an important way to treat heart attacks. More tests will need to be done and human trials planned," said advisor to the Singapore researchers, Lee Chuen-Neng, M.D., who heads National University Hospital of Singapore's Department of Cardiac, Thoracic and Vascular Surgery. He also is Chair of Surgery at the National University Health System.

This discovery is all the more significant because the therapy for reperfusion injury remains an unmet need despite three decades of huge resource investment, thousands of research papers and hundreds of experimental protocols. This preclinical study had come amidst an international call to improve the translation of preclinical experimental therapies for reperfusion injury to clinical applications.

Heart attack or myocardial infarction (MI), occurs when blood flow to part of the heart is blocked, and the heart muscle is deprived of oxygen. If allowed to persist, prolonged oxygen deprivation causes cell death and irreversible loss of heart function, and inevitably progresses to heart failure and death. To minimise heart muscle damage and preserve the pumping action of the heart after a MI, early reperfusion by standard medical treatments such as angioplasty (commonly known as "ballooning") or bypass surgery is carried out in the hospital. Despite this, most MI patients suffer additional irreversible cardiac muscle cell loss, ironically as a result of these treatments — a condition known as reperfusion injury.

As Singapore moves from basic science towards translational studies in the next phase of its biomedical push, rigorous preclinical testing and carefully designed studies such as this project would be most critical in ensuring the success of clinical trials.

Professor Birgit Lane, IMB's Executive Director, said:

"This is a very exciting result from Dr. Lim and her colleagues. It paves the way for improved recovery after heart attack – a very practical outcome from stem cell research. It is a great example of what can be achieved when doctors and scientists work closely together. By sharing their specialist skills and knowledge, they can discover and refine new approaches to curing sick people. This targeting of research to find ways of combating illness and benefiting people faster is at the heart of what we aim to do at IMB."
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Snuppy Get Puppies!

Snuppy Get Puppies
Saturday, 06 September 2008

Snuppy, the Afghan hound that was produced by cloning in 2005 have recently produced a litter of puppies by the laboratory, once headed by Hwang Woo-suk, who fell from grace in South Korea after two of his papers on cloning human embryonic stem cells were discovered to be fake.

The Afghan hound impregnated two cloned bitches of the same breed through artificial insemination, a Seoul National University (SNU) research team said in a statement last week.

"This is the first time in the world that puppies have been born from cloned parents," team leader Lee Byung-Chun told AFP.

One of the 10 puppies, which were born between May 14 and 18, died but nine others are healthy, he said.

"This shows the reproductive ability of a cloned dog," Lee said.

Lee's team, which says it also produced the world's first cloned wolves, plans to carry out a similar breeding experiment with them.
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NSA Releases New Guidelines for hESC Research

Updated guidelines for human embryonic stem cell research released
Friday, 05 September 2008

2008 Amendments to the National Academies' Guidelines for H ...
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The National Academies today released amended guidelines for research involving human embryonic stem cells, revising those that were issued in 2005 and updated in 2007. The Academies originally produced the guidelines to offer a common set of ethical standards for the responsible conduct of research using human stem cells, an area that, due to an absence of comprehensive federal funding, was lacking national standards. Since their initial release, the guidelines have served effectively as the basis for oversight of this research in the United States. In addition, a standing advisory committee — a joint project between the Academies' National Research Council and Institute of Medicine — was established to monitor and review scientific advances and determine any need for revisions.

Embryonic stem cells have the potential to produce all of the body's cell types. Researchers are working to harness stem cells' ability both to regenerate themselves and produce specialized cells that may lead to medical treatments that replace certain types of cells damaged or lost to debilitating illness and injury, such as nerve cells.

One reason for the 2008 modifications is to provide guidance on the derivation and use of new human stem cells that were first developed last year. These cells — called "induced pluripotent cells" — are made by reprogramming non-embryonic adult cells into a stem-cell-like state, in which they can be manipulated to form a wide array of specialized body cells. Although induced pluripotent stem cells can be derived without using embryos, the ethical and policy concerns related to their potential uses are similar to those pertaining to human embryonic stem cells. For example, issues arising from mixing human and animal cells in a single organism are relevant for stem cells from both embryonic and non-embryonic sources. However, derivation of induced pluripotent stem cells does not require special stem cell expertise and is adequately covered by current Institutional Review Board regulations, the report says.

At this time it is still undetermined which stem cell types will prove the most useful for regenerative medicine, as most likely each will have some utility, noted the committee that wrote the report. Therefore, the need for research with human embryonic stem cells still exists despite the availability of new cell sources.

The amended guidelines also clarify that "direct expenses" for reimbursement to women donating their eggs for use in stem cell research may include costs associated with travel, housing, child care, medical care, health insurance, and actual lost wages. This language extends the 2005 guidelines, which stated that women who undergo hormonal induction to generate eggs specifically for research purposes should be reimbursed only for "direct expenses" incurred as a result of the procedure, although they did not specify which expenses qualified as direct. The committee stressed that reimbursement for lost wages is not a payment for eggs; the intent is to leave all donors neither better off nor worse off financially.

To instil a high level of confidence that institutions and their researchers are conducting stem cell research responsibly, the guidelines recommend that the public be informed about the types of stem cell research under way and how the research conforms to the institution's established procedures. Moreover, the committee strongly suggested as a good management practice that institutions conducting human embryonic stem cell research carry out periodic audits of their embryonic stem cell research oversight (ESCRO) committees to ensure proper performance and make the findings of the audits available to the public. The audits should document decisions regarding the acceptance of research proposals and verify that cell lines in use were acceptably derived.

Additionally, the new guidelines clarify that an institutional ESCRO committee may conduct expedited review for research done exclusively in a laboratory dish or test tube that does not create new lines of stem cells but uses previously derived human embryonic stem cell lines. The original guidelines stated that research is "permissible after currently mandated review and proper notification of the relevant research institution." However, the word "notification" led some experts to question if the requirement could be fulfilled by merely informing ESCRO committees that the research would occur. Although allowing for expedited review, the guidelines still require an ESCRO committee to determine if the human embryonic stem cells have been acceptably derived.

Future committee deliberations will consider items for which additional information-gathering and more extensive debate and discussion may be necessary. For example, the National Institutes of Health determined that the human embryonic stem cell lines declared in 2001 by President George W. Bush to be eligible for federally funded research were derived from embryos donated with informed consent and without financial inducement. Based on this determination, the Academies' 2007 guidelines had deemed those lines to have been acceptably derived. However, questions about their derivation were raised when this report was near completion. In addition, a breakthrough in the ability to "reprogram" adult cells from one type to another in a living animal was recently announced. The committee will continue to monitor developments in stem cell research to decide whether any future changes to the guidelines are warranted.

2008 AMENDMENTS TO THE NATIONAL ACADEMIES' GUIDELINES FOR HUMAN EMBRYONIC STEM CELL RESEARCH are available from the National Academies Press.
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What is a gene?

Study offers tool for communicating genetics to public
Friday, 05 September 2008

Even scientists define 'a gene' in different ways, so it comes as little surprise that the media also have various ways of framing the concept of a gene, according to a new study appearing in the October 2008 issue of EMBO reports.

The study, Frame that gene, is based on the analysis of 300 articles in British and Norwegian newspapers: The Guardian, The Sun and The Daily Mail from the UK; and Aftenposten, Dagbladet, and VG from Norway.

The researchers — a molecular biologist, a media expert and a PhD student in science communication from the University of Oslo, Norway — identified five main 'gene frames' in different types of media. For example, the "deterministic" frame, which was particularly evident in tabloid media, involves one-dimensional conclusions along the lines of "Drunk? It's in your genes". According to the authors of the study, this may be related to the desire of journalists to sell a story by keeping it simple and accessible. In contrast, the "evolutionary" frame, commonly used by scientists, gives more insight, but may be difficult to communicate. Moreover, the study also found that the gene has become a playful metaphor, for example by stating that "Mazda has many Ford genes".

The analysis in EMBO reports shows that journalists present the term 'gene' — either consciously or subconsciously — using a number of different frames that may invoke various prejudiced images in the reader's mind.

"Such a diversity of meanings presents a key challenge to science communications, so both scientists and journalists could benefit from a clear classification of the polysemy," the paper argues.

The authors hope that their novel approach will be a useful tool for journalists and scientists to improve their explanations of genetics for a broader audience and better understand how scientific topics are framed in the mass media.

"The common understanding of scientific topics is increasingly important because the public is more and more able to influence policy-making on scientific issues and thus the funding and even the nature of research itself", explained Rebecca Carver from the Institute of Basic Medical Science at the University of Oslo and the first author of the study. Ferocious debates on genetically modified crops or stem cell research illustrate the importance that genetics and molecular biology have gained in everyday life.

The study publication Frame that Gene: A tool for Analyzing and Classifying the Communication of Genetics to the Public will appear in the October issue of EMBO reports.

Reference:
Frame that gene. A tool for analysing and classifying the communication of genetics to the public.
Rebecca Carver, Ragnar Waldahl & Jarle Breivik
EMBO reports AOP. Published online: 5 September 2008, doi:10.1038/embor.2008.176
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Cancer Gets Its Complexity Scrutinized

Studies spot numerous undiscovered gene alterations in pancreatic and brain cancers
Thursday, 04 September 2008

It has long been understood among cancer researchers, that tumours are almost an individualized genetic disease. However, the complexity of the genetic changes occurring while a tumour is growing has not been possible to appreciate, even less study before. Now, several studies are aiming at exactly this goal: to get a complete genetic picture of cancers and tumours, of the same group individualised.

Maps of individual breast cancer and colorectal cancer genomes were published last year, in part by a team at the Johns Hopkins Kimmel Cancer Center. Now, the same team has deciphered the complete genetic blueprint for lethal pancreatic cancer and brain cancer.

Believed to be the most comprehensive result to date for any tumour type, the new map evaluated mutations in virtually all known human protein-encoding genes, comprised of more than 20,000 genes, in 24 pancreatic cancers and 22 brain cancers.

A core set of regulatory gene processes and pathways, about a dozen for each tumour type, were found to be altered in the majority of tumours studied by the researchers. In pancreatic cancer, these 12 pathways, including those linked to DNA damage control, cell maturation, and tumour invasion, were altered in 67 percent to 100 percent of tumours.

"This perspective changes the way we think about solid tumours and their management, because drugs or other agents that target the physiologic effects of these pathways, rather than individual gene components, are likely to be the most useful approach for developing new therapies," says Bert Vogelstein, M.D., co-director of the Ludwig Center at Johns Hopkins and a Howard Hughes Medical Institute investigator.

In addition to the pathway discoveries, a number of individual mutated genes were identified, including 83 cancer genes in pancreatic cancer and 42 in the most lethal form of brain cancer, glioblastoma multiforme (GBM). Additionally, 70 genes that were dramatically over-expressed in either cancer encode proteins that are on the surface of cells or secreted, making them potential diagnostic and screening targets.

A parallel study from the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard, together with their collaborating investigators at 18 institutions and organizations, report an array of broken, missing, and overactive genes — some implicated for the first time — in glioblastoma, the most common and deadly form of adult brain cancer.

The large-scale combing of the brain cancer genome confirms the key roles of some previously known mutated genes and implicates a variety of other genetic changes that may be targets for future therapies.

References:
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
D. Williams Parsons, Siân Jones, Xiaosong Zhang, Jimmy Cheng-Ho Lin, Rebecca J. Leary, Philipp Angenendt, Parminder Mankoo, Hannah Carter, I-Mei Siu, Gary L. Gallia, Alessandro Olivi, Roger McLendon, B. Ahmed Rasheed, Stephen Keir, Tatiana Nikolskaya, Yuri Nikolsky, Dana A. Busam, Hanna Tekleab, Luis A. Diaz Jr., James Hartigan, Doug R. Smith, Robert L. Strausberg, Suely Kazue Nagahashi Marie, Sueli Mieko Oba Shinjo, Hai Yan, Gregory J. Riggins, Darell D. Bigner, Rachel Karchin, Nick Papadopoulos, Giovanni Parmigiani, Bert Vogelstein, Victor E. Velculescu, and Kenneth W. Kinzler
Published online September 4 2008; 10.1126/science.1164382

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Siân Jones, Xiaosong Zhang, D. Williams Parsons, Jimmy Cheng-Ho Lin, Rebecca J. Leary, Philipp Angenendt, Parminder Mankoo, Hannah Carter, Hirohiko Kamiyama, Antonio Jimeno, Seung-Mo Hong, Baojin Fu, Ming-Tseh Lin, Eric S. Calhoun, Mihoko Kamiyama, Kimberly Walter, Tatiana Nikolskaya, Yuri Nikolsky, James Hartigan, Douglas R. Smith, Manuel Hidalgo, Steven D. Leach, Alison P. Klein, Elizabeth M. Jaffee, Michael Goggins, Anirban Maitra, Christine Iacobuzio-Donahue, James R. Eshleman, Scott E. Kern, Ralph H. Hruban, Rachel Karchin, Nickolas Papadopoulos, Giovanni Parmigiani, Bert Vogelstein, Victor E. Velculescu, and Kenneth W. Kinzler
Published online September 4 2008; 10.1126/science.1164368

Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network
Nature advance online publication 4 September 2008, doi:10.1038/nature07385

Articles from EurekAlert!:
Comprehensive genetic blueprints revealed for lethal pancreatic, brain cancers
The Cancer Genome Atlas reports first results of comprehensive study of brain tumours
Parsing the genome of a deadly brain tumor
Studies spot numerous undiscovered gene alterations in pancreatic and brain cancers
Massive cancer gene search finds potential new targets in brain tumors
Collaboration between researchers yields more comprehensive portrait of brain cancer
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All Forms of Stem Cell Research Needed

Researchers Push Need for All Forms of Stem Cell Research
Thursday, 04 September 2008

In light of a recent breakthrough study in adult stem cell research published in Nature, a group of the world’s leading researchers, the International Society for Stem Cell Research (ISSCR), cautions against discounting the potential benefits of all forms of stem cell research, adult and embryonic alike.

The study, conducted at the Harvard Stem Cell Institute by Dr. Douglas Melton, co-director of the Institute and a founding member of the ISSCR, demonstrated in mice that a non-insulin producing cell in the pancreas could be diverted to produce insulin through a process called “direct reprogramming”.

“There is no question that this study represents a great advance in the field of regenerative medicine,” said Dr. George Q. Daley, ISSCR past-president and associate director of the Stem Cell Program at Children’s Hospital Boston.

“But as Dr. Melton himself has emphatically stated, this advance does not negate the role of research with induced pluripotent stem cells (iPS) or human embryonic stem cells. In fact, embryonic stem cell research provides science with the very foundation and insights that make advances like this study possible. There is no question that embryonic and all adult forms of stem cell research must continue if we are to realize the full promise of regenerative medicine.”

Although iPS cells themselves represent a major technological advance, studies with embryonic stem cells will remain essential to ultimately advancing the potential of iPS cells for clinical application.

“We are continuing to do research using human embryonic stem cells and iPS cells,” Dr. Douglas Melton explained.

“We would not be where we are today without having worked with human embryonic stem cells. These unique cells provide a window into human development and disease development that is needed if we are to make further progress in understanding and treating chronic diseases. Embryonic stem cells remain the key to long-term progress in this field.”

While transforming adult cells directly from one specialized type to another is a huge leap in stem cell research, scientists warn that it may be years before the technology could translate into cures for chronic diseases in humans, and that there are still many barriers to overcome. There is hope that these experiments in mice will be translatable to humans. However, testing would involve manipulations now carefully managed by the FDA and the Institutional Review Boards that oversee the use of humans in experimental therapies. In such manipulations, the virus that delivers the reprogramming genes could pose dangers to patients at this point, and more research is needed. In the meantime, researchers continue to pursue all avenues of stem cell research in their efforts to alleviate debilitating conditions.

The International Society for Stem Cell Research (ISSCR) is an independent, non-profit membership organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application.
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Changes to Embryonic Stem Cells Caused by Down Syndrome

Changes to Embryonic Stem Cells Caused by Down Syndrome
Thursday, 04 September 2008

Scientists investigating the mechanisms of Down Syndrome (DS) have revealed the earliest developmental changes in embryonic stem cells caused by an extra copy of human chromosome 21 – the aberrant inheritance of which results in the condition. Their study is published online today (Thursday 4 September) in the American Journal of Human Genetics.

Lead by Dean Nizetic, Professor of Cellular and Molecular Biology at Barts and The London School of Medicine and Dentistry, the team utilised embryonic stem cells from a previously genetically engineered species of mice carrying a copy of human chromosome 21. They discovered that extra chromosome 21 - a genetic state known as trisomy 21 - disturbs a key regulating gene called NRSF or REST, which in turn disturbs the cascade of other genes that control normal development at the embryonic stem cell stage. Furthermore, they identified one gene (DYRK1A) on human chromosome 21, whose overdose in trisomy (DS) is responsible for the observed effects.

Down Syndrome belongs to the group of conditions called 'aneuploidies', defined by an abnormal loss or gain of genetic material, i.e. fragments of chromosomes or whole chromosomes. Aneuploidies cause congenital anomalies that are a prime cause of infant death in Europe and the USA, and are currently on the increase with advancing maternal age in European countries. The number of people with DS in Europe exceeds half a million. The condition is more common than muscular dystrophy and cystic fibrosis. However, the development of new therapeutic concepts is hindered by the fact that unlike muscular dystrophy and cystic fibrosis, where a single mutated gene causing the disease is known, the entire human chromosome 21 (containing around 300 genes) still has to be dissected into individual gene-dose contributions to the DS symptoms.

Professor Nizetic, calling for further research into the components of the disturbed cascade he and his team have revealed said:

"We hope that further research might lead to clues for the design of new therapeutic approaches tackling developmental delay, mental retardation, ageing and regeneration of brain cells, and Alzheimer's disease. In other words, we hope our work will open new routes to tackle the genetics of these health disorders, approaching them from the "back entrance", as dominant component-symptoms of Down Syndrome."

Reference:
DYRK1A-Dosage Imbalance Perturbs NRSF/REST Levels, Deregulating Pluripotency and Embryonic Stem Cell Fate in Down Syndrome
Claudia Canzonetta, Claire Mulligan, Samuel Deutsch, Sandra Ruf, Aideen O'Doherty, Robert Lyle, Christelle Borel, Nathalie Lin-Marq, Frederic Delom, Jürgen Groet, Felix Schnappauf, Serena De Vita, Sharon Averill, John V. Priestley, Joanne E. Martin, Janet Shipley, Gareth Denyer, Charles J. Epstein, Cristina Fillat, Xavier Estivill, Victor L.J. Tybulewicz, Elizabeth M.C. Fisher, Stylianos E. Antonarakis, Dean Nizetic
The American Journal of Human Genetics, 04 September 2008, 10.1016/j.ajhg.2008.08.012
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Structure of Key Epigenetic Component Identified

'Open source' data-sharing policy facilitates trio of papers
Wednesday, 03 September 2008

Scientists from the Structural Genomics Consortium (SGC) have determined the 3D structure of a key protein component involved in enabling "epigenetic code" to be copied accurately from cell to cell.

Epigenetic code is a series of chemical switches that is added onto our DNA in order to ensure that the cells in our body can form different types of tissue, for example liver and skin, despite having identical DNA genetic code.

When DNA is copied from cell to cell, it is essential that the epigenetic code is also copied accurately. If not, a liver cell may divide into another type of cell, such as a nerve or eye cell. A breakdown in this system might also mean that a gene for cell growth is accidentally switched on, for example, leading to unregulated cell growth and the development of tumours.

Research published in 2007 showed the importance of the nuclear protein UHRF1 in ensuring that the epigenetic code is accurately copied. Epigenetic switches are created by the addition of a chemical group (methyl) to DNA in a process known as methylation, facilitated by the enzyme DNMT1. The researchers believe that when this code is copied, UHRF1 ensures the accuracy of the process, like a proof-reader checks a typeset article before printing.

The key element of UHRF1 involved in this "proofreading" process is known as the Set and Ring Associated (SRA) domain, but the exact mechanisms by which the SRA domain accomplishes this task were unclear. Today, in three different articles, the journal Nature publishes the structure of the key element of UHRF1 that facilitates this process.

"Given the increasing focus on epigenetics as a mechanism behind cancer, elucidating the structure of UHRF1 may provide crucial insights into what goes wrong," says Professor Sirano Dhe-Paganon from the Structural Genomics Consortium laboratories at the University of Toronto, Canada.

The structural papers not only represent an advance for the epigenetics field, but also an advance for how the science was done. The concurrent publication of the three papers highlights the competitive nature of this field, but in fact these papers were made possible because the SGC, in keeping with its policy of making its data freely and immediately available, made the underlying information available in the Protein Data Bank late in 2007. The availability of this information allowed the other groups to make more rapid progress in their own work.

"By releasing the structural information into the public databases as soon as it was available, we have ensured that other research groups could make immediate and maximum benefit from the shared knowledge," says Professor Dhe-Paganon.

Professor Masahiro Shirakawa from Kyoto University, Japan, openly acknowledges that the SGC data was crucial to his team's paper, which also appears in today's edition of Nature.

"We would like to express our gratitude to the researchers at the SGC for making their available on net," says Professor Shirakawa.

"Structural biology is a complex, but very important field, with the potential to drive forward important research in many areas. The information provided by the SGC significantly speeded up our own work."

The SGC's "open source" policy contrasts with the accepted practice in the structural biology field, which is to make the underlying data available only after the work appears in print. However, Professor Al Edwards, Director of the SGC, believes strongly that data such as the 3D structure of proteins should be made freely available as soon as they are discovered.

"From the outset, it's been important to us to release our structural data immediately," says Professor Edwards.

"This is contrary to the way many scientists work, but we believe it is crucial for facilitating scientific and medical progress, and our policy has not inhibited our ability to publish our work in the top journals. All the protein structures studied by the SGC have medical relevance and making them freely available ensures that scientists are able to use them to make progress in our understanding of disease and the development of new drugs."
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

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Hearing Restoration May be Possible

Cochlear repair after transplant of human cord blood cells
Wednesday, 03 September 2008

According to an Italian research team publishing their findings in the current issue of Cell Transplantation, hearing loss due to cochlear damage may be repaired by transplantation of human umbilical cord hematopoietic stem cells (HSC) since they show that a small number migrated to the damaged cochlea and repaired sensory hair cells and neurons.

For their study, the team used animal models in which permanent hearing loss had been induced by intense noise, chemical toxicity or both. Cochlear regeneration was only observed in animal groups that received HSC transplants.

Researchers used sensitive tracing methods to determine if the transplanted cells were capable of migrating to the cochlea and evaluated whether the cells could contribute to regenerating neurons and sensory tissue in the cochlea.

"Our findings show dramatic repair of damage with surprisingly few human-derived cells having migrated to the cochlea," said Roberto P. Revoltella, MD, PhD, lead author of the study.

"A fraction of circulating HSC fused with resident cells, generating hybrids, yet the administration of HSC appeared to be correlated with tissue regeneration and repair as the cochlea in non-transplanted mice remained seriously damaged."

Results also showed that cochlear regeneration was less in the transplanted group deafened by noise rather than chemicals, implying that damage were more severe when induced by noise. Regenerative effects were greater in mice injected with a higher number of HSC. They also found that regeneration of cochlear tissues improved as time passed.

According to Revoltella, their results suggest the possibility of an "emerging strategy for inner ear rehabilitation… providing conditions for the resumption of deafened cochlea."

"This study provides hope for a potential treatment for the repair of hearing impairments, particularly those arising as a consequence of cochlear damage," said David Eve, PhD, at the University of South Florida Health, and associate editor of Cell Transplantation.
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

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Cardiac Cell Transplant

Studies show promise in cardiac tissue repair
Wednesday, 03 September 2008

Two studies published in the current issue of Cell Transplantation examine the efficacy of transplanting bone marrow cells (BMCs) for the repair of heart tissue.

The first study found that implanting adult cardiomyocytes (heart muscle cells) in combination with BMCs has two advantages over transplanting cardiomyocytes alone. First, while cardiac function was preserved by implanting cardiomyocytes alone, the therapeutic effects of transplanting them along with bone marrow cells was enhanced. Second, programmed cell death (apoptosis) of the host cardiomyocytes was reduced significantly after the implantation of BMCs alone or in combination with cardiomyocytes when compared with results after the implanting of cardiomyocytes alone.

"Our findings indicate that cardiomyocytes and bone marrow cells can assist and compliment each other," said the study's lead author Tao-sheng Li, MD, PhD of the Department of Surgery and Clinical Science at the Yamaguchi University Graduate School of Medicine.

"This technique shows promise as a feasible new strategy for myocardial repair."

Cardiomyocyte survival was counted at one, three and seven days after culture to see if protection against apoptosis was successful.

Cardiac function was measured before and 28 days after treatment. Results showed that cardiomyocyte survival increased significantly in the co-cultured group. Although cardiomyocytes shrank as the post-culture time was extended, morphological change was milder in the co-cultured group.

The second study, carried out at the University of Padua, compared transplantation of two sources of mensenchymal stem cells (MSCs) – derived from bone marrow (BM-MSCs) and from foetal amniotic fluid (AF-MSCs) – to discover which type of cell was most effective in replenishing damaged rat heart tissues.

"The choice of stem cell type to be used in therapeutic cardiovascular regeneration of acute or chronic myocardial ischemia could be of paramount importance if specific combinations of differentiated cell phenotypes are to be obtained," said Severio Sartore, PhD, the study's lead author.

The study found that "the capability of both MSCs to be converted to CM-like cells (cardiomyocyte or heart muscle cells) is quite low and many cells appear with more than one nucleus."

It was unclear to researchers whether those cells had divided or fused. Furthermore, although both MSCs have "similar biological profiles" they did not possess equal differentiation potential.

"The differentiation potentials of MSCs observed in vitro need a definitive in vivo confirmation for future cell therapy experiments aimed at replenishing damaged cardiovascular tissue," concluded Sartore and his team.

"While the two MSCs can contribute roughly at the same extent to capillary formation, AF-MSCs are not able to participate in the formation of arterioles and hence to vascular SMCs (smooth muscle cells)."

Sartore noted that in previous studies when AF-MSCs were transplanted into porcine models of myocardial ischemia they were converted to vascular cells, but not to cardiomyocytes.

"Both of these papers further help delineate the evolving role of bone marrow in cardiac cell therapy, not only as a regenerative means but also supportive to other cells and tissues" said Amit N. Patel, M.D., director of cardiovascular regenerative medicine and associate professor of surgery at the University of Utah School of Medicine, and a section editor for Cell Transplantation.
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

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EU Call for Ban on Animal Cloning for Food

EU Call for Ban on Animal Cloning for Food
Wednesday, 03 September 2008

The European Parliament members called for a ban in the EU on the cloning of animals for food supply. MEPs also urged an embargo on imports of cloned animals, their offspring and products derived from these sources. In a resolution adopted by 622 MEPs in favour, 32 against and 25 abstentions, the House calls on the Commission "to submit proposals prohibiting for food supply purposes:

• the cloning of animals,
• the farming of cloned animals or their offspring,
• the placing on the market of meat or dairy products derived from cloned animals or their offspring, and
• the importing of cloned animals, their offspring, semen and embryos from cloned animals or their offspring, and meat or dairy products derived from cloned animals or their offspring."

Animal health problems and risks for the European quality model
The text refers to the health, welfare and higher mortality problems of cloned animals and their surrogate dams recently highlighted by several groups of European experts, including the European Food Safety Authority (EFSA) and the European Group on Ethics. MEPs also stress that cloning would significantly reduce genetic diversity within livestock populations, increasing the possibility of whole herds being decimated by diseases to which they are susceptible.

In addition, the European Parliament fears that use of cloning techniques would harm the image of the European agricultural model, which is based on product quality, environment-friendly principles and respect for stringent animal welfare conditions. They also point out that Directive 98/58/EC on the protection of farm animals bans natural or artificial procedures which are likely to cause suffering or injury to any of the animals concerned.

Currently no products derived from cloned animals are sold in Europe or the rest of the world. However, experts believe that such products could reach the market by 2010. A moratorium on the sale of this type of product, introduced in the USA in 2001, was challenged by the US Food and Drug Administration, which concluded in January that meat and milk from clones of cattle, pigs and goats and their offspring are as reliable as those of traditionally bred animals.

European Commission quizzed
During their debate yesterday evening, MEPs quizzed the European Commission on its position and its plans as regards animal cloning.

"Not only is it a case of food safety, we in Europe believe that we are producing food quality products", EP Agriculture Committee Chairman Neil Parish (EPP-ED, UK) said.

"It is also a question of animal welfare and consumer confidence" and there is a "risk of producing less strong and healthy animals".

He stressed "we have to look at this seriously".

Mr Parish said: "Cloning entails serious health and welfare problems for clones and their surrogate dams; animal health problems come from invasive techniques required to produce a clone; there is the suffering of surrogate dams which carry cloned foetuses, and high levels of ill health and mortality in early life for cloned animals. I call on the Commission to submit proposals prohibiting the cloning of animals in the food supply and the placing of cloned animals on the market in meat and dairy products."

Androula Vassiliou, the Commissioner for health and food safety, said that the Commission was closely following scientific developments in this area and "is aware that even though the efficiency of animal cloning has improved over the last years, adverse health effects on animal health and welfare still occur today".

The Commission "is now evaluating the necessary steps to be taken" and "takes ethical considerations fully into account", including the opinion of the European Group of Ethics which "advocated that at the moment there are no convincing arguments to justify the production of food from clones and their offspring".

"According to global trade rules, imports of food products from third countries might be suspended if they present a serious threat to animal or public health. On the basis of the studies conducted and the opinion of EFSA, the Commission will consider whether restrictions must be imposed", she added.
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

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Barack Obama on Stem Cell Research

Barack Obama on Stem Cell Research
Tuesday, 02 September 2008

US Presidential candidate Barack Obama has spelled out his views on several main scientific issues, in responses to a science policy survey issued by research and science advocacy group ScienceDebate2008. Members of Sciencedebate2008 include Nobel laureates Peter Agre, David Baltimore, and Steve Chu, along with former science advisors to the president Neil Lane and John Gibbons. There are also university presidents, and the editors of both Science and Nature, among others.

The Democratic presidential nominee provided lengthy answers to 14 questions on topics from climate change and national security to stem cell research and scientific integrity, voicing support for basic research and for confronting issues such as energy independence, combating global warming, and bolstering the economy through science and technology innovation.

On stem cell research, he said:

"I strongly support expanding research on stem cells. I believe that the restrictions that President Bush has placed on funding of human embryonic stem cell research have handcuffed our scientists and hindered our ability to compete with other nations. As president, I will lift the current administration's ban on federal funding of research on embryonic stem cell lines created after August 9, 2001 through executive order, and I will ensure that all research on stem cells is conducted ethically and with rigorous oversight."

On the benefits and potential risks of genetic information, he commented:

"I have been a long-time supporter of the recently passed Genetic Information Non-Discrimination Act. In addition, concerned about the premature introduction of genetic testing into the public domain without appropriate oversight, I introduced the Genomics and Personalized Medicine Act of 2007 aimed at ensuring the safety and accuracy of such testing."

See also:
Obama Reverses Bush’s Stem Cell Policy
CellNEWS - Monday, 09 March 2009
Obama to Reverse Embryonic Stem Cell Ban
CellNEWS - Saturday, 07 March 2009
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

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US Republicans at Odds Over Human Embryo Research

Stem cells research divides McCain and his VP choice
Monday, 01 September 2008

By changing one little word, the committee drafting the Republican 2008 election platform last week proposed banning all human embryo research in the United States, whether publicly or privately funded.

John McCain, the presumptive Republican presidential nominee, is under no obligation to follow the party platform — which is a statement of principle with no binding power — but the change highlights the already noticeable contrast between him and the official party position. Although his running mate, Governor Sarah Palin of Alaska, opposes human embryonic stem cell research, McCain has twice voted to loosen restrictions on federal funding of the work.

On 27 August, the Republican Platform Committee approved an amendment by Mary Summa of North Carolina, one of its 100 or so delegates. It changed "and" to "or" so that the platform now calls for a ban on "the creation of or experimentation on human embryos for research purposes" (emphasis added). The change is expected to win final approval during the Republican convention this week in St Paul, Minnesota.

See more at:
Republicans at odds over human embryo research
Nature, 1 September 2008, doi:10.1038/455012a
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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/ and
http://www.geocities.com/giantfideli/index.html

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