Stroke victims may benefit from stem cell transplants

Stroke victims may benefit from stem cell transplants Monday, 28 January 2008 According to two studies published in the current issue of Cell Transplantation (Vol.16 No.10), stroke victims may benefit from human mesenchymal stem cell (hMSC) or bone marrow stromal cell (BMSCs) transplantation. In both studies, the migration of chemically “tagged” transplanted stem cells were tracked to determine the degree to which the transplanted cells reached damaged areas of the brain and became therapeutically active. Tracking transplanted hMSCs to infarcted areas In a study carried out by Korean researchers, labelled hMSCs (early precursor cells to musculoskeletal, blood, vascular and urogenital systems) were transplanted into animal stroke models with cerebral artery occlusion and tracked by magnetic resonance imaging (MRI) at two days, one week, two weeks, six weeks and ten weeks after transplant. “Cells started showing indications of migration as early as one or two weeks following transplantation,” said lead author Jihwan, Song, DPhil, of the Pochon CHA University College of Medicine. “At 10 weeks, the majority of the cells were detected in the core of the infarcted area.” The study concluded that there is a strong tendency for transplanted hMSCs to migrate toward the infarcted area regardless of injection site but that the degree of migration was likely based on differences in each animal’s ischemic condition. “We speculate that the extensive migratory nature of stem cells and their utilization will provide an important tool for developing novel stroke therapies,” said Song. BMSCs migrate to damaged brain tissue, improve neural function In a joint Canadian, Chinese study, BMSCs — connective tissue cells — were injected into animals 24 hours following middle cerebral artery occlusion. Using laser scanning confocal microscopy to track fluorescent signals and immune markers attached to the cells, researchers found that within seven days of the injection the BMSCs had migrated through the region of the middle cerebral artery into the scar area and border zone of the ischemic region. “We evaluated vascular density in the ischemic region in all animals seven days after cell transplantation,” said study lead author Ren-Ke Li, MD, PhD. “The animals exhibited significant reductions in scar size and cell death and improvements in neurological function when compared to controls that received no BMSCs.” Researchers concluded that the intravenous delivery of bone marrow-derived cells may enhance tissue repair and, in turn, functional recovery after a stroke. While the potential mechanisms for this recovery are unclear, among the possibilities are that the brain microenvironment early on following a stroke may mimic brain development. Subsequent elevated levels of growth factors might enhance homing of BMSCs to the injured area and induce cell proliferation. “Our results support the potential therapeutic use of BMSCs after a stroke,” concluded Li. Editor’s comments: “Both studies lend important support to a growing body of laboratory evidence that bone marrow is a remarkable adult stem cell source for transplant therapy following stroke,” says Cell Transplantation associate editor Cesar V. Borlongan, Ph.D. of the Medical College of Georgia. “The non-invasive MRI visualization of pre-labeled BMSCs could become a routine clinical marker for transplanted cells as well as for safety and efficacy.” ......... ZenMaster

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Synthetic Bacterial Genome

Venter Institute Scientists Create First Synthetic Bacterial Genome Publication Represents Largest Chemically Defined Structure Synthesized in the Lab Team Completes Second Step in Three Step Process to Create Synthetic Organism Friday, 25 January 2008 A team of 17 researchers at the J. Craig Venter Institute (JCVI) has created the largest man-made DNA structure by synthesizing and assembling the 582,970 base pair genome of a bacterium, Mycoplasma genitalium JCVI-1.0. This work, published online today in the journal Science by Dan Gibson, Ph.D., et al, is the second of three key steps toward the team’s goal of creating a fully synthetic organism. In the next step, which is ongoing at the JCVI, the team will attempt to create a living bacterial cell based entirely on the synthetically made genome.

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M. genitalium: Living Organism with the Smallest Genome.

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The team achieved this technical feat by chemically making DNA fragments in the lab and developing new methods for the assembly and reproduction of the DNA segments. After several years of work perfecting chemical assembly, the team found they could use homologous recombination (a process that cells use to repair damage to their chromosomes) in the yeast Saccharomyces cerevisiae to rapidly build the entire bacterial chromosome from large subassemblies. “This extraordinary accomplishment is a technological marvel that was only made possible because of the unique and accomplished JCVI team,” said J. Craig Venter, Ph.D., President and Founder of JCVI. “Ham Smith, Clyde Hutchison, Dan Gibson, Gwyn Benders, and the others on this team dedicated the last several years to designing and perfecting new methods and techniques that we believe will become widely used to advance the field of synthetic genomics.” The building blocks of DNA — adenine (A), guanine (G), cytosine (C) and thiamine (T) — are not easy chemicals to artificially synthesize into chromosomes. As the strands of DNA get longer they get increasingly brittle, making them more difficult to work with. Prior to today’s publication the largest synthesized DNA contained only 32,000 base pairs. Thus, building a synthetic version of the genome of the bacteria M. genitalium genome that has more than 580,000 base pairs presented a formidable challenge. However, the JCVI team has expertise in many technical areas and a keen biological understanding of several species of mycoplasmas. “When we started this work several years ago, we knew it was going to be difficult because we were treading into unknown territory,” said Hamilton Smith, M.D., senior author on the publication. “Through dedicated teamwork we have shown that building large genomes is now feasible and scalable so that important applications such as biofuels can be developed.” Methods for Creating the Synthetic M. genitalium The process to synthesize and assemble the synthetic version of the M. genitalium chromosome began first by resequencing the native M. genitalium genome to ensure that the team was starting with an error free sequence. After obtaining this correct version of the native genome, the team specially designed fragments of chemically synthesized DNA to build 101 “cassettes” of 5,000 to 7,000 base pairs of genetic code. As a measure to differentiate the synthetic genome versus the native genome, the team created “watermarks” in the synthetic genome. These are short inserted or substituted sequences that encode information not typically found in nature. Other changes the team made to the synthetic genome included disrupting a gene to block infectivity. To obtain the cassettes the JCVI team worked primarily with the DNA synthesis company Blue Heron Technology, as well as DNA 2.0 and GENEART.

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Circular map of the M. genitalium chromosome. Genes are coloured according to the functional classification of the encoded proteins. The length of each projection is proportional to the number of amino acid residues in the respective protein. The outside ring shows the products of the genes that are transcribed clockwise, and the inside ring shows those transcribed counter clockwise.

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From here, the team devised a five stage assembly process where the cassettes were joined together in subassemblies to make larger and larger pieces that would eventually be combined to build the whole synthetic M. genitalium genome. In the first step, sets of four cassettes were joined to create 25 subassemblies, each about 24,000 base pairs (24kb). These 24kb fragments were cloned into the bacterium Escherichia coli to produce sufficient DNA for the next steps, and for DNA sequence validation. The next step involved combining three 24kb fragments together to create 8 assembled blocks, each about 72,000 base pairs. These 1/8th fragments of the whole genome were again cloned into E. coli for DNA production and DNA sequencing. Step three involved combining two 1/8th fragments together to produce large fragments approximately 144,000 base pairs or 1/4th of the whole genome. At this stage the team could not obtain half genome clones in E. coli, so the team experimented with yeast and found that it tolerated the large foreign DNA molecules well, and that they were able to assemble the fragments together by homologous recombination. This process was used to assemble the last cassettes, from 1/4 genome fragments to the final genome of more than 580,000 base pairs. The final chromosome was again sequenced in order to validate the complete accurate chemical structure. The synthetic M. genitalium has a molecular weight of 360,110 kilodaltons (kDa). Printed in 10 point font, the letters of the M. genitalium JCVI-1.0 genome span 147 pages.

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This handout photo from the J. Craig Venter Institute shows a single molecule from the synthetic Mycoplasma genitalium bacteria over a period of 0.6 seconds. US scientists have taken a major step toward creating the first ever artificial life form by synthetically reproducing the DNA of a bacteria.

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“This is an exciting advance for our team and the field. However, we continue to work toward the ultimate goal of inserting the synthetic chromosome into a cell and booting it up to create the first synthetic organism,” said Dan Gibson, lead author. The research to create the synthetic M. genitalium JCVI-1.0 was funded by Synthetic Genomics, Inc. Key Milestones in JCVI’s Synthetic Genomics Research The work described by Gibson et al. has its genesis in research by Dr. Venter and colleagues in the mid-1990s after sequencing M. genitalium and beginning work on the minimal genome project. This area of research, trying to understand the minimal genetic components necessary to sustain life, began with M. genitalium because it is a bacterium with the smallest genome that we know of that can be grown in pure culture. That work was published in the journal Science in 1995. In 2003 Drs. Venter, Smith and Hutchison made the first significant strides in the development of a synthetic genome by their work in assembling the 5,386 base pair bacteriophage ΦX174 (phi X). They did so using short, single strands of synthetically produced, commercially available DNA (known as oligonucleotides) and using an adaptation of polymerase chain reaction (PCR), known as polymerase cycle assembly (PCA), to build the phi X genome. The team produced the synthetic phi X in just 14 days. In June 2007 another major advance was achieved when JCVI researchers led by Carole Lartigue, Ph.D., announced the results of work on genome transplantation methods allowing them to transform one type of bacteria into another type dictated by the transplanted chromosome. The work was published in the journal Science, and outlined the methods and techniques used to change one bacterial species, Mycoplasma capricolum, into another, Mycoplasma mycoides Large Colony (LC), by replacing one organism’s genome with the other one’s genome. Genome transplantation was the first essential enabling step in the field of synthetic genomics as it is a key mechanism by which chemically synthesized chromosomes can be activated into viable living cells. Today’s announcement of the successful synthesis of the M. genitalium genome is the second step leading to the next experiments to transplant a fully synthetic bacterial chromosome into a living organism and “boot up” the cell. Ethical Considerations Since the beginning of the quest to understand and build a synthetic genome, Dr. Venter and his team have been concerned with the societal issues surrounding the work. In 1995 while the team was doing the research on the minimal genome, the work underwent significant ethical review by a panel of experts at the University of Pennsylvania (Cho et al, Science December 1999:Vol. 286. no. 5447, pp. 2087 – 2090). The bioethical group's independent deliberations, published at the same time as the scientific minimal genome research, resulted in a unanimous decision that there were no strong ethical reasons why the work should not continue as long as the scientists involved continued to engage public discussion. Dr. Venter and the team at JCVI continue to work with bioethicists, outside policy groups, legislative members and staff, and the public to encourage discussion and understanding about the societal implications of their work and the field of synthetic genomics generally. As such, the JCVI’s policy team, along with the Center for Strategic & International Studies (CSIS), and the Massachusetts Institute of Technology (MIT), were funded by a grant from the Alfred P. Sloan Foundation for a 20-month study that explored the risks and benefits of this emerging technology, as well as possible safeguards to prevent abuse, including bioterrorism. After several workshops and public sessions the group published a report in October 2007 outlining options for the field and its researchers. About the J. Craig Venter Institute The JCVI is a not-for-profit research institute dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 400 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The legacy organizations of the JCVI are: The Institute for Genomic Research (TIGR), The Center for the Advancement of Genomics (TCAG), the Institute for Biological Energy Alternatives (IBEA), the Joint Technology Center (JTC), and the J. Craig Venter Science Foundation. The JCVI is a 501 (c)(3) organization. Publication: Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome Published Online January 24, 2008Science DOI: 10.1126/science.1151721

Links: J. Craig Venter Institute Synthetic biology for energy production Mycoplasma genitalium genome More from CellNEWS: Venter makes synthetic life... or not yet? October 09, 2007 Next Step Towards Artificial Life Whole Genome Transplantation Achieved in Mycobacterium June 28, 2007 Venter attempt at the minimalistic approach of creating ‘artificially-made’ life November24, 2002 ......... ZenMaster

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China New Powerhouse of World's Economy and Innovation

Time to Move Over, US! Thursday, 24 January 2008 A new study of worldwide technological competitiveness suggests China may soon rival the United States as the principal driver of the world’s economy – a position the US has held since the end of World War II. If that happens, it will mark the first time in nearly a century that two nations have competed for leadership as equals. The study’s indicators predict that China will soon pass the United States in the critical ability to develop basic science and technology, turn those developments into products and services – and then market them to the world. Though China is often seen as just a low-cost producer of manufactured goods, the new “High Tech Indicators” study done by researchers at the Georgia Institute of Technology clearly shows that the Asian powerhouse has much bigger aspirations. “For the first time in nearly a century, we see leadership in basic research and the economic ability to pursue the benefits of that research – to create and market products based on research – in more than one place on the planet,” said Nils Newman, co-author of the National Science Foundation-supported study. “Since World War II, the United States has been the main driver of the global economy. Now we have a situation in which technology products are going to be appearing in the marketplace that were not developed or commercialized here. We won’t have had any involvement with them and may not even know they are coming.” Georgia Tech has been gathering the high tech indicators since the mid-1980s, when the concern was which country would be the “next Japan” as a competitive producer and exporter of technology products. The current “HTI-2007” information was gathered for use in the NSF’s biennial report, “Science and Engineering Indicators,” the most recent of which was released January 15. Georgia Tech’s “High Tech Indicators” study ranks 33 nations relative to one another on “technological standing,” an output factor that indicates each nation’s recent success in exporting high technology products. Four major input factors help build future technological standing: national orientation toward technological competitiveness, socioeconomic infrastructure, technological infrastructure and productive capacity. Each of the indicators is based on a combination of statistical data and expert opinions. A chart showing change in the technological standing of the 33 nations is dominated by one feature – a long and continuous upward line that shows China moving from “in the weeds” to world technological leadership over the past 15 years.

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Chart shows the change in technological standing for several nations from 1993 to 2007.

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The 2007 statistics show China with a technological standing of 82.8, compared to 76.1 for the United States, 66.8 for Germany and 66.0 for Japan. Just 11 years ago, China’s score was only 22.5. The United States peaked in 1999 with a score of 95.4. “China has really changed the world economic landscape in technology,” said Alan Porter, another study co-author and co-director of the Georgia Tech Technology Policy and Assessment Center, which conducted the research. “When you take China’s low-cost manufacturing and focus on technology, then combine them with the increasing emphasis on research and development, the result ultimately won’t leave much room for other countries.” The United States and Japan have both fallen in relative technological standing – though not absolute measures – because of the dramatic rise of China and other nations such as the “Asian Tigers:” South Korea, Singapore and Taiwan. Japan has faltered a bit over time, and if the increasingly-integrated European Union were considered one entity instead of 27 separate countries, it would surpass the United States. “We are seeing consistent gains for China across all the criteria we measure,” Newman said. “As a percentage mover relative to everyone else, we have not seen a stumble for China. The gains have been dramatic, and there is no real sense that any kind of levelling off is occurring.” Most industrialized countries reach a kind of equilibrium in the study, moving up slightly in one data set, or down slightly in another. But the study shows no interruptions in China’s advance. Recent statistics for the value of technology products exported – a key component of technological standing – put China behind the United States by the amount of “a rounding error:” about $100 million. If that trend continues, Newman noted, China will shortly pass the United States in that measure of technological leadership. China’s emphasis on training scientists and engineers – who conduct the research needed to maintain technological competitiveness – suggests it will continue to grow its ability to innovate. In the United States, the training of scientists and engineers has lagged, and post-9/11 immigration barriers have kept out international scholars who could help fill the gap. “For scientists and engineers, China now has less than half as many as we do, but they have a lot of growing room,” noted Newman. “It would be difficult for the United States to get much better in this area, and it would be very easy for us to get worse. It would be very easy for the Chinese to get better because they have more room to manoeuvre.” China is becoming a leader in research and development, Porter noted. For instance, China now leads the world in publications on nanotechnology, though US papers still receive more citations. On the input indicators calculated for 2007, China lags behind the United States. In “national orientation,” China won a score of 62.6, compared to 78.0 for the United States. In “socioeconomic infrastructure,” China rated 61.2, compared to 87.9 for the United States. In the other two factors, China also was behind the US, 60.0 versus 95.5 for “technological infrastructure” and 85.2 versus 93.4 for “productive capacity.” China has been dramatically improving its input scores, which portends even stronger technological competitiveness in the future. “It’s like being 40 years old and playing basketball against a competitor who’s only 12 years old – but is already at your height,” Newman said. “You are a little better right now and have more experience, but you’re not going to squeeze much more performance out. The future clearly doesn’t look good for the United States.” .........

ZenMaster

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Pancreatic Stem Cells Found in Adult Mice

Pancreatic Stem Cells Found in Adult Mice Thursday, 24 January 2008 Just as many scientists had given up the search, researchers have discovered that the pancreas does indeed harbour stem cells with the capacity to generate new insulin-producing beta cells. If the finding made in adult mice holds for humans, the newfound progenitor cells will represent “an obvious target for therapeutic regeneration of beta cells in diabetes,” the researchers report in the Jan. 25 issue of Cell, a publication of Cell Press. “One of the most interesting characteristics of these [adult] progenitor cells is that they are almost indistinguishable from embryonic progenitors,” said Harry Heimberg of the JDRF Center at Vrije Universiteit Brussel in Belgium and the JDRF Center for Beta Cell Therapy in Diabetes. “In terms of their structure and gene expression, there are no major differences. They look and behave just like embryonic beta cell progenitors." Insulin is required for cells to take up blood sugar, the body’s primary energy source. In people with certain types of diabetes, blood sugar rises due to an inability of pancreatic beta cells to produce insulin in sufficient quantities. Previous studies had failed to demonstrate the existence of bona fide beta cell progenitors in the pancreas after birth. The elusiveness of this cell type reached a summit when genetic lineage tracing provided evidence that pre-existing beta cells, rather than stem/progenitor cells, are the major source of new beta cells in adult mice, the researchers said. “Most people gave up looking because they are so few and so hard to activate,” Heimberg said. In the new study, Heimberg’s team tied off a duct that drains digestive enzymes from the pancreas. That injury led to a doubling of beta cells in the pancreas within two weeks, they showed. The animals’ pancreases also began producing more insulin, evidence that the new beta cells were fully functional, Heimberg said. He suspects the regenerative process is sparked by an inflammatory response in the enzyme-flooded pancreas. They further found that the production of new beta cells depends on a gene called Neurogenin 3 (Ngn3), which is known to play a role in the pancreas during embryonic development. “The most important challenge now is to extrapolate our findings to patients with diabetes,” Heimberg said. Although he cautioned that any potential diabetes treatment remains far into the future, “our findings reveal the significance of investigating the feasibility of (1) isolating facultative beta cell progenitors and newly formed beta cells from human pancreas in order to expand and differentiate them in vitro and transplant them in diabetic patients and (2) composing a mix of factors able to activate beta cell progenitors to expand and differentiate in situ in patients with an absolute or relative deficiency in insulin,” the researchers wrote. Reference: β Cells Can Be Generated from Endogenous Progenitors in Injured Adult Mouse Pancreas ......... ZenMaster

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Spain Approves Therapeutic Cloning Projects

Three research projects have been given permission, two in Valencia and one in Madrid Thursday, 24 January 2008 Typically Spanish report that the Spanish Commission for the Control of the Donation and Use of Human Stem Cells, a body which depends on the Ministry for Health and Consumer Affairs, has given the green light to the first project in Spain which will use the technique known as nucleus transfer. This is therapeutic cloning to obtain lines of stem cells which are prepared specifically from the patient. The research is led by Miodrag Stojkovic at the Centro Prínciple Felipe de Valencia, and is intended to investigate the molecular bases of two neurological illnesses, child epilepsy and hereditary palsy. Stojkovic was the first European scientist who managed to clone a human embryo from embryonic stem cells. The Ministry for Health has also given its support to two other studies, one in Valencia and another in Madrid, but the final approval still has to be obtained from the regional governments in each region. Links: Spain gives go ahead to research using therapeutic cloning Valencia Stem Cell Bank ......... ZenMaster

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International Human Genome Project Launched

Three-year study will produce most detailed map of human genetic variation Wednesday, 23 January 2008 An international research consortium today announced the 1000 Genomes Project, an ambitious effort that will involve sequencing the genomes of at least a thousand people from around the world to create the most detailed and medically useful picture to date of human genetic variation. The project will receive major support from the Wellcome Trust Sanger Institute in Hinxton, England, the Beijing Genomics Institute, Shenzhen (BGI Shenzhen) in China and the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH). Drawing on the expertise of multidisciplinary research teams, the 1000 Genomes Project will develop a new map of the human genome that will provide a view of biomedically relevant DNA variations at a resolution unmatched by current resources. As with other major human genome reference projects, data from the 1000 Genomes Project will be made swiftly available to the worldwide scientific community through freely accessible public databases. “The 1000 Genomes Project will examine the human genome at a level of detail that no one has done before,” said Richard Durbin, Ph.D., of the Wellcome Trust Sanger Institute, who is co-chair of the consortium. “Such a project would have been unthinkable only two years ago. Today, thanks to amazing strides in sequencing technology, bioinformatics and population genomics, it is now within our grasp. So we are moving forward to build a tool that will greatly expand and further accelerate efforts to find more of the genetic factors involved in human health and disease.” Any two humans are more than 99 percent the same at the genetic level. However, it is important to understand the small fraction of genetic material that varies among people because it can help explain individual differences in susceptibility to disease, response to drugs or reaction to environmental factors. Variation in the human genome is organized into local neighbourhoods called haplotypes, which are stretches of DNA usually inherited as intact blocks of information. Recently developed catalogues of human genetic variation, such as the HapMap, have proved valuable in human genetic research. Using the HapMap and related resources, researchers already have discovered more than 100 regions of the genome containing genetic variants that are associated with risk of common human diseases such as diabetes, coronary artery disease, prostate and breast cancer, rheumatoid arthritis, inflammatory bowel disease and age-related macular degeneration. However, because existing maps are not extremely detailed, researchers often must follow those studies with costly and time-consuming DNA sequencing to help pinpoint the precise causative variants. The new map would enable researchers to more quickly zero in on disease-related genetic variants, speeding efforts to use genetic information to develop new strategies for diagnosing, treating and preventing common diseases. The scientific goals of the 1000 Genomes Project are to produce a catalogue of variants that are present at 1 percent or greater frequency in the human population across most of the genome, and down to 0.5 percent or lower within genes. This will likely entail sequencing the genomes of at least 1,000 people. These people will be anonymous and will not have any medical information collected on them, because the project is developing a basic resource to provide information on genetic variation. The catalogue that is developed will be used by researchers in many future studies of people with particular diseases. “This new project will increase the sensitivity of disease discovery efforts across the genome five-fold and within gene regions at least 10-fold,” said NHGRI Director Francis S. Collins, M.D., Ph.D. “Our existing databases do a reasonably good job of cataloguing variations found in at least 10 percent of a population. By harnessing the power of new sequencing technologies and novel computational methods, we hope to give biomedical researchers a genome-wide map of variation down to the 1 percent level. This will change the way we carry out studies of genetic disease.” With current approaches, researchers can search for two types of genetic variants related to disease. The first type is very rare genetic variants that have a severe effect, such as the variants responsible for causing cystic fibrosis and Huntington’s disease. To find these rare variants, which typically affect fewer than one in 1,000 people, researchers often must spend years on studies involving affected families. However, most common diseases, such as diabetes and heart disease, are influenced by more common genetic variants. Most of these common variants have weak effects, perhaps increasing risk of a common condition by 25 percent or less. Recently, using a new approach known as a genome-wide association study, researchers have been able to search for these common variants. “Between these two types of genetic variants — very rare and fairly common — we have a significant gap in our knowledge. The 1000 Genomes Project is designed to fill that gap, which we anticipate will contain many important variants that are relevant to human health and disease,” said David Altshuler, M.D., Ph.D., of Massachusetts General Hospital in Boston and the Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard University in Cambridge, Mass., who is the consortium’s co-chair and was a leader of the HapMap Consortium. One use of the new catalogue will be to follow up genome-wide association studies. Investigators who find that a part of the genome is associated with a disease will be able to look it up in the catalogue, and find almost all variants in that region. They will then be able to conduct functional studies to see whether any of the catalogued variants directly contribute to the disease. The 1000 Genomes Project builds on the human haplotype map developed by the International HapMap Project. The new map will provide genomic context surrounding the HapMap’s genetic variants, giving researchers important clues to which variants might be causal, including more precise information on where to search for causal variants. Going a major step beyond the HapMap, the 1000 Genomes Project will map not only the single-letter differences in people’s DNA, called single nucleotide polymorphisms (SNPs), but also will produce a high-resolution map of larger differences in genome structure called structural variants. Structural variants are rearrangements, deletions or duplications of segments of the human genome. The importance of these variants has become increasingly clear with surveys completed in the past 18 months that show these differences in genome structure may play a role in susceptibility to certain conditions, such as mental retardation and autism. In addition to accelerating the search for genetic variants involved in susceptibility to common diseases, the map produced by the 1000 Genomes Project will provide a deeper understanding of human genetic variation and open the door to many other new findings of significance to both medicine and basic human biology. The sequencing work will be carried out at the Sanger Institute, BGI Shenzhen and NHGRI’s Large-Scale Sequencing Network, which includes the Broad Institute of MIT and Harvard; the Washington University Genome Sequencing Center at the Washington University School of Medicine in St. Louis; and the Human Genome Sequencing Center at the Baylor College of Medicine in Houston. The consortium may add other participants over time. The European Bioinformatics Institute (EBI), working with long-term collaborator the US National Institute of Biotechnology Information (NCBI), will make the data swiftly available to the worldwide scientific community through freely available public databases. The EBI and NCBI will collect and analyse sequence generated by the Wellcome Trust Sanger Institute, the Beijing Genomics Institute, Shenzhen, China, and the USA’s National Human Genome Research Institute Large-Scale Sequencing Network. The project depends on large-scale implementation of several new sequencing platforms. Using standard DNA sequencing technologies, the effort would likely cost more than $500 million. However, leaders of the 1000 Genomes Project expect the costs to be far lower – in the range of $30 million to $50 million – because of the project’s pioneering efforts to use new sequencing technologies in the most efficient and cost-effective manner. In the first phase of the 1000 Genomes Project, lasting about a year, researchers will conduct three pilots. The results of the pilots will be used to decide how to most efficiently and cost effectively produce the project’s detailed map of human genetic variation. The first pilot will involve sequencing the genomes of two nuclear families (both parents and an adult child) at deep coverage that averages 20 passes of each genome. This will provide a comprehensive dataset from six people that will help the project figure out how to identify variants using the new sequencing platforms, and serve as a basis for comparison for other parts of the effort. The second pilot will involve sequencing the genomes of 180 people at low coverage that averages two passes of each genome. This will test the ability to use low-coverage data from new sequencing platforms to identify sequence variants and to put them in their genomic context. The third pilot will involve sequencing the coding regions, called exons, of about 1,000 genes in about 1,000 people. This is aimed at exploring how best to obtain an even more detailed catalogue in the approximately 2 percent of the genome that is comprised of protein-coding genes. During its two-year production phase, the 1000 Genomes Project will deliver sequence data at an average rate of about 8.2 billion bases per day, the equivalent of more than two human genomes every 24 hours. The volume of data – and the interpretation of those data – will pose a major challenge for leading experts in the fields of bioinformatics and statistical genetics. “This project will examine the human genome in a detail that has never been attempted – the scale is immense. At 6 trillion DNA bases, the 1000 Genomes Project will generate 60-fold more sequence data over its three-year course than have been deposited into public DNA databases over the past 25 years,” said Gil McVean, Ph.D., of the University of Oxford in England, one of the co-chairs of the consortium’s analysis group. “In fact, when up and running at full speed, this project will generate more sequence in two days than was added to public databases for all of the past year.” The 1000 Genomes Project will use samples from volunteer donors who gave informed consent for their DNA to be analyzed and placed in public databases. NHGRI and its partners will follow the extensive and careful ethical procedures established for previous projects. As was the case for the International HapMap Project and Human Genome Project, the 1000 Genomes Project will have an expert working group devoted to examining the ethical, legal and social issues related to its research. The first thousand samples for the 1000 Genomes Project will come from those used for the HapMap and from additional samples in the extended HapMap set, which used the same collection processes. No medical or personal identifying information was obtained from the donors, and the samples are labelled only by the population from which they were collected. The donors’ anonymity was enhanced by recruiting more donors than were actually used. Similar processes will be used for collecting additional samples for the 1000 Genomes Project. Among the populations whose DNA will be sequenced in the 1000 Genomes Project are: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States. “This project reinforces our commitment to transform genomic information into tools that medical research can use to understand common disease,” said Jun Wang, Ph.D., associate director of BGI Shenzhen, whose laboratory will participate in the 1000 Genomes Project and which also took part in the HapMap Project. “It will benefit all nations by creating a valuable resource for researchers around the globe.” The detailed map of human genetic variation will be used by many researchers seeking to relate genetic variation to particular diseases. In turn, such research will lay the groundwork for the personal genomics era of medicine, in which people routinely will have their genomes sequenced to predict their individual risks of disease and response to drugs. The data generated by the 1000 Genomes Project will be held by and distributed from the European Bioinformatics Institute and the National Center for Biotechnology Information, which is part of NIH. There will also be a mirror site for data access at BGI Shenzhen. In addition to a catalogue of variants, the data will include information about surrounding variation that can speed identification of the most important variants. Links:

• 1,000 Genomes Project Web Site
• Wellcome Trust Sanger Institute
• National Human Genome Research Institute
• Beijing Genomics Institute, Shenzhen
• HapMap Web Site
• European Bioinformatics Institute
• NCBI
• Personal Genome Project

References: Genomics sizes up: China launches large-scale human sequencing initiative Knome Lands Two Customers for Whole-Genome Sequencing ......... ZenMaster

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Deutsche Forschungsgemeinschaft Skeptical of Human Cloning

Priority is given to reprogramming research Wednesday, 23 January 2008 According to a paper published in the journal Stem Cells, an American group has succeeded in inserting cell nuclei from human skin cells into human enucleated oocytes and to stimulate these new cells to undergo cell division in the laboratory. This may constitute the first step on the way towards cloning human cells. Many issues relating to the method employed remain unclear at present. The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) already expressed its scepticism regarding the process of “therapeutic cloning” or “research cloning” when it released a statement on the issue of stem cell research in the autumn of 2006. Both for scientific reasons, and because this method calls for a large number of eggs from young donors, the DFG has given clear priority to research into reprogramming methods. Developments since late 2006 have confirmed the DFG´s stance. Research done by American and Japanese groups, for example, has shown that it is possible to convert human skin cells back into cells similar to stem cells by treating them with reprogramming factors. The DFG is also very critical of recent findings in the field of “research cloning in the human system”. Experiments of this kind are prohibited in Germany, as is importing cloned cell lines. The DFG has no intention of changing its current position. Rather, the DFG continues to support research into the reprogramming of adult and embryonic stem cells. ......... ZenMaster

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Embryonic Stem Cell Transplantation Improves Muscular Dystrophy in Mice

Embryonic Stem Cell Transplantation Improves Muscular Dystrophy in Mice Sunday, 20 January 2008 Using embryonic stem cells from mice, UT Southwestern Medical Center researchers have prompted the growth of healthy – and more importantly, functioning – muscle cells in mice afflicted with a human model of Duchenne muscular dystrophy. The study represents the first time transplanted embryonic stem cells have been shown to restore function to defective muscles in a model of muscular dystrophy. The researchers’ newly developed technique, which involves stringent sorting to preserve all stem cells destined to become muscle, avoids the risk of tumour formation while improving the overall muscle strength and coordination of the mice, the researchers found. The mice used in the study lacked dystrophin, the same protein that humans with the fatal wasting disease also are missing. The study, headed by Dr. Rita Perlingeiro, assistant professor of developmental biology and molecular biology, is available online today and in the February issue of Nature Medicine. “We envision eventually developing a stem-cell therapy for humans with muscular dystrophy, if we are able to successfully combine this approach with the technology now available to make human embryonic stem cells from reprogrammed skin cells,” Dr. Perlingeiro said. “These cells can be transplanted into the muscle, and they cause muscle regeneration resulting in stronger contractility.” The study represents a major step in the field, she said, because the researchers were able to tease out exactly the cells they wanted. “The problem had been that embryonic stem cells make everything,” Dr. Perlingeiro said. “They make a great variety of cells. The trick is to pull out only the one type you want.” The UT Southwestern researchers focused on manipulating genes that are active in the very early stages as embryonic stem cells start to develop into more specialized cells. At first, they activated a gene called Pax3, which is involved in creating muscle cells, and then injected those cells into the animals’ muscles. Those cells caused tumours containing many different types of cells, indicating that there were still residual undifferentiated embryonic stem cells in the cultures at the time of implantation. “Even if there are 10 undesirable cells, that’s too many,” Dr. Perlingeiro said. The researchers then began using fluorescent dyes to sort cells depending on whether some surface markers were turned on while others were turned off. By analogy, it was as if they were dealing with a crowd of people and wanted to pull out only those with red hair, green scarves and blue coats, while those with red hair, green scarves and no coats would be disqualified. The final selection of cells, containing only one type, was again injected into the animals’ hind-limb muscles. After a month, the fluorescent dyes showed that the cells had deeply penetrated the muscle, an indication that they were growing and reproducing as desired, and many of the muscle fibres also contained dystrophin, the key protein lacking in muscular dystrophy. After three months, the mice also showed no signs of tumours. Tests of isolated muscles showed that the treated muscles were significantly stronger than untreated mice lacking dystrophin, although not quite as strong as those of normal mice. The treated mice also were tested for coordination. Again, their performance was better than that of untreated mice, but not as good as that of normal mice. “The improved coordination is significant because it shows the embryonic stem cells have benefited the animal’s quality of life, not simply caused an isolated growth with no overall improvement,” Dr. Perlingeiro said. The researchers will next investigate whether these transplanted cells can make “muscle stem cells,” which are partially developed cells in muscle tissue that serve as a reserve to replenish muscles. They also are testing their implantation approach in animal models of other types of muscular dystrophy. ......... ZenMaster

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Batten Disease Trial Girl Dies

Batten Disease Trial Girl Dies Saturday, 19 January 2008 San José Mercury News report that a girl aged 9 has died, who participated in an experimental stem cell treatment for Batten disease. It is believed so far that she died of natural progression of her disease and not from any adverse reactions to the treatment. About a year ago, she had been injected in her brain with foetal neural stem cells, in an attempt to replace cells that makes the enzyme Batten disease children lack in their brain cells. Five other children, all under 13 years of age, have participated in the same study at the Oregon Health & Science University's Doernbecher Children's Hospital. Link: Girl dies, had tried stem cell therapy ......... ZenMaster

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Stem Cell Research Aims to Tackle Parkinson's Disease

New ways to grow brain cells in the laboratory could eventually provide a way to treat Parkinson's disease. Friday, 18 January 2008 Scientists in Sweden are developing new ways to grow brain cells in the laboratory that could one day be used to treat patients with Parkinson’s disease, an international conference of biologists organised by the European Science Foundation (ESF) was told last week. Professor Ernest Arenas of the Karolinska Institute in Stockholm presented his research to the EuroSTELLS “Stem Cell Niches” conference in Barcelona on January 11. Stem cell therapy hold the promise of treating disease by growing new tissues and organs from stem cells – ‘blank’ cells that have the potential to develop into fully mature or ‘differentiated’ cells. The EuroSTELLS is an ESF EURCORES programme, managed by the European Medical Research Councils (EMRC), that aims to develop a stem cell ‘toolbox’ by generating fundamental knowledge on stem cell biology. Parkinson’s disease affects around three in a hundred of people aged over 65. The condition can cause muscles to become rigid and limbs to tremble uncontrollably. Parkinson’s disease results from the loss of a particular type of brain cell called dopaminergic (DA) neurons in the part of the brain called the substantia nigra. Among the various approaches that are currently being discussed from an ethical perspective, is the possible approach of taking stem cells, growing them into new brain cells and transplanting these into the patient. “The idea is to start with stem cells and induce them to become neurons,” said Professor Arenas, whose research is carried out as part of a EuroSTELLS collaboration. “These could then be transplanted into the brain of the patient. Also, such cells could be ideal for developing and testing new drugs to treat brain disease.” However, to create such cells that function efficiently and safely is a major challenge. Early efforts at growing DA neurons from embryonic stem cells produced cells which, when transplanted into animal models, had a tendency to form tumours or clumps, or die without an obvious reason. Professor Arenas’ team studied the development of DA neurons in animals to determine the important biological molecules in the brain that were necessary for the cells to grow and function efficiently. The scientists identified one particular molecule that seemed to be key, a protein called Wnt5a. They showed that when this molecule, together with a second protein called noggin, was included in cultures of stem cells, far more DA neurons were produced than when these ingredients were not present. The team then carried out a series of molecular, chemical and electrophysiological tests on the newly grown neurons to check their proficiency, which was shown to be good. Crucially the team also moved away from embryonic stem cells – which can be induced to grow into a wide variety of different cells. Instead they used neural stem cells – which are programmed to develop only into nerve cells. When the researchers transplanted the cells into laboratory animals whose substantia nigra region of the brain was damaged, the results were promising. “We reversed almost completely the behavioural abnormalities, and neurons differentiated, survived and re-innervated the relevant part of the brain better” Professor Arenas said. “Furthermore we do not see the kind of proliferation of the cells that has occurred in the past and we get very little clustering when the cells are treated with Wnt5a. The cells are safer than embryonic stem cells and more efficient than foetal tissue.” Verification of this approach with human cells is ongoing and if the study is successful, it may lead to a clinical trial. Experts in the field have recently identified this approach as the next step in cell replacement therapy for Parkinson’s disease and the hope is that this may, ultimately, lead to cells suitable for transplant into human patients. ......... ZenMaster

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UK HFEA Approves Human-Animal Hybrid Embryo Research

UK HFEA Approves Human-Animal Hybrid Embryo Research Friday, 18 January 2008 The Human Fertilisation and Embryology Authority (HFEA) yesterday granted permission to two groups of scientists to create human-animal embryos for research. Two centres, King's College London and Newcastle University, will now be able to begin their work under one-year research licences. Scientists from the two centres submitted applications last year to create human stem cells using animal eggs. The process involves injecting an empty cow or rabbit egg with human DNA. A burst of electricity is then used to trick the egg into dividing, so that it becomes a very early embryo from which stem cells can be extracted. "The HFEA License Committee determined that the two applications satisfied all the requirements of the law," the agency said. Scientists want to create hybrid embryos by merging human cells with animal eggs in a bid to extract stem cells. The embryos would then be destroyed within 14 days. At the moment, scientists in the UK have to rely on human eggs left over from fertility treatment, but they are in short supply and are not always good quality. Dr Stephen Minger and colleagues at King's College London want to create hybrids to study diseases known to have genetic causes — such as Alzheimer's disease, spinal muscular atrophy and Parkinson's disease. Dr. Lyle Armstrong's team at The Northeast England Stem Cell Institute, Newcastle University, are planning to use the technique to help understand how stem cells differentiate into different tissues in the body. Dr Armstrong said: "Now that we have the licence we can start work as soon as possible.” "We have already done a lot of the work by transferring animal cells into cow eggs so we hope to make rapid progress." "Finding better ways to make human embryonic stem cells is the long-term objective of our work and understanding reprogramming is central to this." "Cow eggs seem to be every bit as good at doing this job as human eggs so it makes sense to use them since they are much more readily available but it is important to stress that we will only use them as a scientific tool and we need not worry about cells derived from them ever being used to treat human diseases." Professor Sir John Gurdon, a Cambridge University researcher who has injected human DNA into frogs' eggs, said: "Scientifically... I'm not persuaded it will work. If you put cells from one species into the egg of another, the egg may divide, but you could get a lot of genetic abnormality that won't lead to good-quality stem cells." Links: HFEA Kings College London Newcastle University ......... ZenMaster

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Human Cloning Achieved?

Human Cloning Achieved? Friday, 18 January 2008 In a research paper from a group in La Jolla, CA and Detroit, MI, scientists describe how they have succeeded in producing a human cloned blastocysts, using freshly donated eggs and adult fibroblasts. Thorough analysis of the DNA and mtDNA in the donor cells and resulting blastocyst cells confirmed that SCNT had occurred. However, no stem cell lines were obtained from this single cloned blastomere, since all the material was used for the DNA analyses. Also, several other attempts to produce cloned embryos failed, not producing any live blastocysts or producing parthenogenetically activated blastocysts. Therefore, the value of the recent study is limited, even though it seams to confirm the possibility of producing cloned human embryos. The generation of patient-specific embryonic stem cells would revolutionize our understanding of human diseases (1). Currently, two different approaches are being studied to derive patient-specific stem cells: somatic cell nuclear transfer (SCNT) and direct reprogramming (2, 3). The recent generation of induced pluripotent stem (iPS) cells has put the feasibility of SCNT in regenerative medicine under intense discussion. However, at this early stage of development, the achievement to make iPS cells can not be considered as a substitute for SCNT. As has been pointed out by many scientists, the use of genes and retroviruses known to cause cancer in mammals and retroviruses known to have the ability to disrupt the normal DNA function and stimulate the birth of cancer cells (4, 5) makes it questionable if iPS cells can ever be used in regenerative medicine, especially cell therapy. Maybe the only use will be in research labs to elucidate small steps in the process of dedifferentiation or redifferentiation. Therefore it is essential to maintain the pace of research on the more ethically controversial areas, such as the use of fresh human oocytes and SCNT. Derivation of human embryos by SCNT remains in its infancy stages, with just a few papers reporting the generation of nuclear transfer human embryos (6-11). However, none of them have resulted in the derivation of nuclear transfer stem cells (NTSC). Clearly, still a number of hurdles, both ethical and technical, need to be overcome if SCNT is to lead to the successful application of patient-specific NTSC in regenerative medicine. In proving that human embryos can be obtained by SCNT, French et al. (12) succeeded in obtaining 5 blastocysts from 21 oocytes using adult somatic cells as karyoplasts. However, the results verified, for the first time through DNA and mtDNA fingerprinting that of the 5 blastocysts only one had the donor cell genomic DNA and the oocyte mtDNA. Considering such a small number of blastocysts, a completely different result may just as well have been reached. The experiment could easily have rendered zero true clones. The final challenge in therapeutic SCNT is still the isolation of NTSC. Once a NTSC line is obtained, a huge amount of cells will be available to carry out all the required studies to prove each clone identity. Firstly then, the process of finding way’s to explore patient-specific embryonic stem cells true potential in regenerative medicine, can start. REFERENCES 1. Cervera RP, Stojkovic M. Human embryonic stem cell derivation and nuclear transfer: impact on regenerative therapeutics and drug discovery. Clin Pharmacol Ther 2007;82:310-315. 2. Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-872. 3. Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007;318:1917-1920. 4. Löwer R. The pathogenic potential of endogenous retroviruses: facts and fantasies. Trends Microbiol 1999;7:350-356. 5. Yi Y, Hahm SH, Lee KH. Retroviral gene therapy: safety issues and possible solutions. Curr Gene Ther 2005;5:25-35. 6. Cibelli JB, Kiessling AA, Cuniff K et al. Somatic cell nuclear transfer in humans: pronuclear and early embryonic development. J Reg Med 2001;2:25-31. 7. Lu C, Lin G, Xie X et al. Reconstruction of human embryos derived from somatic cells. Chin Science Bull 2003;48:1840-1843. 8. Stojkovic M, Stojkovic P, Leary C et al. Derivation of a human blastocyst after heterologous nuclear transfer to donated oocytes. Reprod Biomed Online 2005;11:226-231. 9. Lavoir MC, Weier J, Conaghan J et al. Poor development of human nuclear transfer embryos using failed fertilized oocytes. Reprod Biomed Online 2005:11:740-744. 10. Hall VJ ,Compton D, Stojkovic P et al. Developmental competence of human in vitro aged oocytes as host cells for nuclear transfer. Hum Reprod 2007;22:52-62. 11. Heindryckx B, De Sutter P, Gerris J et al. Embryo development after successful somatic cell nuclear transfer to in vitro matured human germinal vesicle oocytes. Hum Reprod 2007;22:1982-1990. 12. French AJ, Adams CA, Anderson LS et al. Development of human cloned blastocysts following somatic cell nuclear transfer (SCNT) with adult fibroblasts. Stem Cells 2008; January 17, doi:10.1634/stemcells.2007-0252 ......... ZenMaster

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CIRM Gets 57 Applications for New hESC Lines Grants

CIRM Gets 57 Applications for New Embryonic Stem Cell Lines Grants Wednesday, 16 January 2008 The California Institute for Regenerative Medicine (CIRM) today announced that it has received and accepted 57 letters of intent for the New Cell Lines Awards. 42 applications were received from non-profit organizations and 15 from for-profit companies. The CIRM New Cell Lines Awards will provide up to $25 million to support the derivation and propagation of new lines of pluripotent human stem cells that will have important research and clinical application for understanding, diagnosing and treating serious injury and disease. Pluripotent stem cells have the potential to play a key role in regenerative medicine and in cell replacement therapies because of their unique ability to renew themselves and their potential to form almost all of the cell types of the body, including muscle, nerve, heart and blood. “We are particularly excited to note that based on the letters of intent we have received there is a good balance between research that derives pluripotent stem cell lines from human embryonic stem cell lines as well as new, highly novel methods such as iPS” stated Alan O. Trounson, Ph.D., the newly appointed president of CIRM. The Awards will fund qualified investigators to conduct research in California that will address the need for new types and sources of human pluripotent stem cell lines and the methods for deriving them. CIRM expects to fund up to 16 New Cell Lines Awards for three years and will support a broad range of research that uses the full spectrum of human cell types and experimental approaches. The Awards will support two categories of research and will give particular consideration to research applications that cannot be currently funded by federal programs:

• Derivation of new human embryonic stem cell lines using excess or rejected early-stage human embryos generated by in vitro fertilization.
• Derivation of pluripotent human stem cell lines from other sources using alternative methods such as, but not limited to, somatic cell nuclear transfer (SCNT) or reprogramming of neonatal or adult cells (iPS cells).

Completed applications for the New Cell Lines Awards are due on February 5, 2008. Review of applications by the Grants Working Group is anticipated for March or April of 2008, with review and approval by the Independent Citizen’s Oversight Committee (ICOC), CIRM’s governing board, projected for June 2008. .........

ZenMaster

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Recreation of Beating Heart in the Laboratory

Method may revolutionize how heart and other organ tissues are developed Monday, 14 January 2008 University of Minnesota researchers have created a beating heart in the laboratory. By using a process called whole organ decellularization, scientists from the University of Minnesota Center for Cardiovascular Repair grew functioning heart tissue by taking dead rat and pig hearts and reseeding them with a mixture of live cells. The research will be published online in the January 13 issue of Nature Medicine. “The idea would be to develop transplantable blood vessels or whole organs that are made from your own cells,” said Doris Taylor, Ph.D., director of the Center for Cardiovascular Repair, Medtronic Bakken professor of medicine and physiology, and principal investigator of the research. Nearly 5 million people live with heart failure, and about 550,000 new cases are diagnosed each year in the United States. Approximately 50,000 United States patients die annually waiting for a donor heart. While there have been advances in generating heart tissue in the lab, creating an entire 3-dimensional scaffold that mimics the complex cardiac architecture and intricacies, has always been a mystery, Taylor said. It seems decellularization may be a solution – essentially using nature’s platform to create a bioartifical heart, she said. Decellularization is the process of removing all of the cells from an organ – in this case an animal cadaver heart – leaving only the extracellular matrix, the framework between the cells, intact. This was done by perfusing the heart with a solution of detergent. After successfully removing all of the cells from both rat and pig hearts, researchers injected them with a mixture of progenitor cells that came from neonatal or newborn rat hearts and placed the structure in a sterile setting in the lab to grow. The results were very promising, Taylor said. Four days after seeding the decellularized heart scaffolds with the heart cells, contractions were observed. Eight days later, the hearts were pumping. “Take a section of this ‘new heart’ and slice it, and cells are back in there,” Taylor said. “The cells have many of the markers we associate with the heart and seem to know how to behave like heart tissue.” “We just took nature’s own building blocks to build a new organ,” said Harald C. Ott, M.D., co-investigator of the study and a former research associate in the center for cardiovascular repair, who now works at Massachusetts General Hospital. “When we saw the first contractions we were speechless.” Researchers are optimistic this discovery could help increase the donor organ pool. In general, the supply of donor organs is limited and once a heart is transplanted, individuals face life-long immunosuppression, often trading heart failure for high blood pressure, diabetes, and kidney failure, Taylor said. Researchers hope that the decellularization process could be used to make new donor organs. Because a new heart could be filled with the recipient’s cells, researchers hypothesize it’s much less likely to be rejected by the body. And once placed in the recipient, in theory the heart would be nourished, regulated, and regenerated similar to the heart that it replaced. “We used immature heart cells in this version, as a proof of concept. We pretty much figured heart cells in a heart matrix had to work,” Taylor said. “Going forward, our goal is to use a patient’s stem cells to build a new heart.” Although heart repair was the first goal during research, decellularization shows promising potential to change how scientists think about engineering organs, Taylor said. “It opens a door to this notion that you can make any organ: kidney, liver, lung, pancreas – you name it and we hope we can make it,” she said. Reference: Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart Harald C Ott, Thomas S Matthiesen, Saik-Kia Goh, Lauren D Black, Stefan M Kren, Theoden I Netoff & Doris A Taylor Published online: 13 January 2008; doi:10.1038/nm1684 ......... ZenMaster

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ACT Make hESC Lines Without Destroying Embryos

ACT Make hESC Lines Without Destroying Embryos 
Thursday, 10 January 2008

Advanced Cell Technology, Inc. together with colleagues announced today the development of five human embryonic stem cell (hESC) lines without the destruction of embryos. These new results have the potential to end the ethical debate surrounding the use of embryos to derive stem cells. In fact, the NIH report to the President refers to this technology as one of the viable alternatives to the destruction of embryos. The new method will be published today in the journal Cell Stem Cells, published by Cell Press. 

The peer-reviewed technique was initially carried out by ACT scientists under the direction of Robert Lanza, M.D., and then independently replicated by scientists on the West Coast. Single cells were removed from the embryos using a technique similar to preimplantation genetic diagnosis (PGD). The biopsied embryos continued to develop normally and were then frozen. The cells that were removed were cultured utilizing a proprietary methodology that recreates the optimal developmental environment, which substantially improved the efficiency of deriving stem cells to rates comparable to using the traditional approach of deriving stem cells from the inner cell mass of a whole blastocyst stage embryo. The stem cells were genetically normal and differentiated into cell types of all three germ layers of the body, including blood cells, neurons, heart cells, cartilage, and other cell types of potentially therapeutic significance. 

“This is a working technology that exists here and now,” said Robert Lanza, M.D., Chief Scientific Officer at Advanced Cell Technology and senior author of the paper. 

“It could be used to increase the number of stem cell lines available to federal researchers immediately. We could send these cells out to researchers tomorrow. If the White House approves this new methodology, researchers could effectively double or triple the number of stem cell lines available within a few months. Too many needless deaths continue to occur while this research is being held up. I hope the President will act now and approve these stem cell lines quickly.” 

 The paper published today also addresses several other important issues. First, the stem cells were derived without culturing multiple cells from each embryo together, and at efficiency levels similar to that reported for conventional stem cell derivation techniques using blastocysts. Second, it addresses ethical objections that the derivation system required co-culture with hESCs from other embryos that were destroyed. The current study demonstrates that hESC co-culture is not an essential part of the derivation procedure. The stem cell lines generated in the present study appear to have the same characteristics as other hESC lines, including expression of the same markers of pluripotency, self-renewing capacity, genetic stability, and ability to differentiate into derivatives of all three germ layers of the body. 

“We are excited that our new method for generating human embryonic stem cell lines without the destruction of embryos has been accepted for inclusion by such a prestigious publication,” said William M. Caldwell IV, Chairman and CEO of Advanced Cell Technology. 

“This new approach addresses the President Bush’s ethical concerns. We are hopeful that the NIH will consider this new approach for federal funding. We believe that such consideration reflects the desire of the American people to bring therapies derived from stem cell research to patients with few or no alternatives.” 

Reference: 
Human Embryonic Stem Cell Lines Generated without Embryo Destruction 
Other contributors to the study and publication include Young Chung and Irina Klimanskaya, Sandy Becker, Tong Li, Marc Maserati, and Shi-Jiang Lu of Advanced Cell Technology; Tamara Zdravkovic, Olga Genbacev, and Susan Fisher of the University of California, San Francisco; and Dusko Ilic and Ana Krtolica of StemLifeLine. 
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Newcastle First to Pay for Human Eggs

IVF Egg Sale Gives Eggs for Therapeutic Cloning Experiments Wednesday, 09 January 2008 Fifteen women undergoing IVF treatment are to take part in a world-first scheme in Newcastle. They are the first to receive IVF treatment at Newcastle's Fertility Centre at Life at a reduced cost in return for donating some eggs for research. They came forward after the North East England Stem Cell Institute (NESCI) received final approval and funding for the scheme known as egg sharing. Under the scheme, women receive about half of the cost of their IVF treatment, £1500, in return for the donation of half their eggs. One hundred women came forward and, after testing and counselling, fifteen were found to be suitable and six begin treatment this month. Scientists at the North East England Stem Cell Institute believe the funding will lead to an increase in the number of eggs for research which could lead to faster progress in stem cell therapies. The project continues over two years. Professor Alison Murdoch who is leading the project at the North East England Stem Cell Institute (NESCI), says: "We are delighted at the excellent response from women in the North East to this important research. We hope that significant progress will be made in the research and that it will also help many couples to have a family from IVF treatment." ABOUT NESCI: The North East England Stem Cell Institute (NESCI) draws together Durham and Newcastle Universities, the Newcastle-upon-Tyne Hospitals NHS Foundation Trust and other partners in a unique interdisciplinary collaboration to convert stem cell research and technologies into cost-effective, ethically-robust 21st century health solutions to ameliorate degenerative diseases, the effects of ageing and serious injury. The Institute has received substantial funding and other support from the Regional Development Agency, One NorthEast and is partly based at the International Centre at Life in Newcastle. ......... ZenMaster

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