Most Complete Human Brain Model to Date Is a ‘Brain Changer’

Once licensed, model likely to accelerate study of Alzheimer’s, autism, more

Wednesday, 19 August 2015

Scientists at The Ohio State University have developed a nearly complete human brain in a dish that equals the brain maturity of a 5-week-old foetus.

The brain organoid, engineered from adult human skin cells, is the most complete human brain model yet developed, said Rene Anand, professor of biological chemistry and pharmacology at Ohio State.

The lab-grown brain, about the size of a pencil eraser, has an identifiable structure and contains 99 percent of the genes present in the human foetal brain. Such a system will enable ethical and more rapid and accurate testing of experimental drugs before the clinical trial stage and advance studies of genetic and environmental causes of central nervous system disorders.

“It not only looks like the developing brain, its diverse cell types express nearly all genes like a brain,” Anand said.

“We’ve struggled for a long time trying to solve complex brain disease problems that cause tremendous pain and suffering. The power of this brain model bodes very well for human health because it gives us better and more relevant options to test and develop therapeutics other than rodents.”

Anand reported on his lab-grown brain Tuesday (Aug. 18) at the 2015 Military Health System Research Symposium in Ft. Lauderdale, Florida.

This image of the lab-grown brain is labelled to

show identifiable structures: the cerebral

hemisphere, the optic stalk and the cephalic

flexure, a bend in the mid-brain region, all

characteristic of the human foetal brain. Credit:

courtesy of The Ohio State University.

Anand, who studies the association between nicotinic receptors and central nervous system disorders, was inspired to pursue a model of human neural biology after encountering disappointing results in a rodent study of an experimental autism drug. Taking a chance with a shoestring budget compared to other researchers doing similar projects, he added stem-cell engineering to his research program. Four years later, he had built himself a replica of the human brain.

The main thing missing in this model is a vascular system. What is there – a spinal cord, all major regions of the brain, multiple cell types, signalling circuitry and even a retina – has the potential to dramatically accelerate the pace of neuroscience research, said Anand, also a professor of neuroscience.

“In central nervous system diseases, this will enable studies of either underlying genetic susceptibility or purely environmental influences, or a combination,” he said.

“Genomic science infers there are up to 600 genes that give rise to autism, but we are stuck there. Mathematical correlations and statistical methods are insufficient to in themselves identify causation. You need an experimental system – you need a human brain.”

Converting adult skin cells into pluripotent cells – immature stem cells that can be programmed to become any tissue in the body – is a rapidly developing area of science that earned the researcher who discovered the technique, Shinya Yamanaka, a Nobel Prize in 2012.

“Once a cell is in that pluripotent state, it can become any organ – if you know what to do to support it to become that organ,” Anand said.

“The brain has been the holy grail because of its enormous complexity compared to any other organ. Other groups are attempting to do this as well.”

Anand’s method is proprietary and he has filed an invention disclosure with the university.

He said he used techniques to differentiate pluripotent stem cells into cells that are designed to become neural tissue, components of the central nervous system or other brain regions.

“We provide the best possible environment and conditions that replicate what’s going on in utero to support the brain,” he said of the work he completed with colleague Susan McKay, a research associate in biological chemistry and pharmacology.

High-resolution imaging of the organoid identifies functioning neurons and their signal-carrying extensions – axons and dendrites – as well as astrocytes, oligodendrocytes and microglia. The model also activates markers for cells that have the classic excitatory and inhibitory functions in the brain, and that enable chemical signals to travel throughout the structure.

It takes about 15 weeks to build a model system developed to match the 5-week-old foetal human brain. Anand and McKay have let the model continue to grow to the 12-week point, observing expected maturation changes along the way.

“If we let it go to 16 or 20 weeks, that might complete it, filling in that 1 percent of missing genes. We don’t know yet,” he said.

He and McKay have already used the platform to launch their own projects, creating brain organoid models of Alzheimer’s and Parkinson’s diseases and autism in a dish. They hope that with further development and the addition of a pumping blood supply, the model could be used for stroke therapy studies. For military purposes, the system offers a new platform for the study of Gulf War illness, traumatic brain injury and post-traumatic stress disorder.

Anand hopes his brain model could be incorporated into the Microphysiological Systems program, a platform the Defense Advanced Research Projects Agency is developing by using engineered human tissue to mimic human physiological systems.

Support for the work came from the Marci and Bill Ingram Research Fund for Autism Spectrum Disorders and the Ohio State University Wexner Medical Center Research Fund.

Anand and McKay are co-founders of a Columbus-based start-up company, NeurXstem, to commercialize the brain organoid platform, and have applied for funding from the federal Small Business Technology Transfer program to accelerate its drug discovery applications.

Source: Ohio State University

Contact: Rene Anand

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Human Gene Patent Invalidated by New York Judge

Patents On Breast Cancer Genes Ruled Invalid In ACLU/PubPat Case
Tuesday, 30 March 2010

Patents on genes associated with hereditary breast and ovarian cancer are invalid, ruled a New York federal court today. The precedent-setting ruling marks the first time a court has found patents on genes unlawful and calls into question the validity of patents now held on approximately 2,000 human genes. The ruling follows a lawsuit brought by a group of patients and scientists represented by the American Civil Liberties Union and the Public Patent Foundation (PUBPAT), a not-for-profit organization affiliated with Benjamin N. Cardozo School of Law.

"Today's ruling is a victory for the free flow of ideas in scientific research," said Chris Hansen, a staff attorney with the ACLU First Amendment Working Group.

"The human genome, like the structure of blood, air or water, was discovered, not created. There is an endless amount of information on genes that begs for further discovery, and gene patents put up unacceptable barriers to the free exchange of ideas."

The ACLU's and PUBPAT's lawsuit against Myriad Genetics and the University of Utah Research Foundation, which hold the patents on the BRCA genes, as well the U.S. Patent and Trademark Office (USPTO), charged that the challenged patents are illegal and restrict both scientific research and patients' access to medical care, and that patents on human genes violate the First Amendment and patent law because genes are "products of nature."

The court today granted the U.S. Patent and Trademark Office's (USPTO) request that it be released as a defendant in the lawsuit. The court found that it was unnecessary to reach the First Amendment claims against the USPTO because it had already ruled in favour of the plaintiffs.

The lawsuit, Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al., was filed on May 12 in the U.S. District Court for the Southern District of New York on behalf of breast cancer and women's health groups, individual women, geneticists and scientific associations representing approximately 150,000 researchers, pathologists and laboratory professionals.

Because the ACLU's lawsuit challenges the whole notion of gene patenting, its outcome could have far-reaching effects beyond the patents on the BRCA genes. Approximately 20 percent of all human genes are patented, including genes associated with Alzheimer's disease, muscular dystrophy, colon cancer, asthma and many other illnesses.

The court recognized the far-reaching impact of the case on medical research and public health. The opinion stated, "…the resolution of the issues presented to this Court deeply concerns breast cancer patients, medical professionals, researchers, caregivers, advocacy groups, existing gene patent holders and their investors, and those seeking to advance public health."

"The court correctly saw that companies should not be able to own the rights to a piece of the human genome," said Daniel B. Ravicher, Executive Director of PUBPAT and co-counsel in the lawsuit.

"No one invented genes. Inventions are specific tests or drugs, which can be patented, but genes are not inventions."

The specific patents the ACLU had challenged are on the BRCA1 and BRCA2 genes. Mutations along the BRCA1 and 2 genes are responsible for most cases of hereditary breast and ovarian cancers. Many women with a history of breast and ovarian cancer in their families opt to undergo genetic testing to determine if they have the mutations on their BRCA genes that put them at increased risk for these diseases. This information is critical in helping these women decide on a plan of treatment or prevention, including increased surveillance or preventive mastectomies or ovary removal.

"We are extremely gratified by this groundbreaking decision," said Sandra Park, staff attorney with the ACLU Women's Rights Project.

"This is the beginning of the end to patents that restrict women's access to their own genetic information and interfere with their medical care."

The patents granted to Myriad give the company the exclusive right to perform diagnostic tests on the BRCA1 and BRCA2 genes and to prevent any researcher from even looking at the genes without first getting permission from Myriad. Myriad's monopoly on the BRCA genes makes it impossible for women to access alternate tests or gets a comprehensive second opinion about their results and allows Myriad to charge a high rate for their tests.

Several major organizations, including the American Medical Association, the March of Dimes and the American Society for Human Genetics, filed friend-of-the-court briefs in support of the challenge to the patents on the BRCA genes.

Attorneys on the case include Hansen and Aden Fine of the ACLU First Amendment Working Group; Park and Lenora Lapidus of the ACLU Women's Rights Project; and Ravicher and Sabrina Hassan of PUBPAT.

Today's decision can be found online at:
www.aclu.org/free-speech-technology-and-liberty-womens-rights/association-molecular-pathology-et-al-v-uspto-et-al.

More information about the case, including an ACLU video featuring breast cancer patients, plaintiff and supporter statements and declarations and the legal complaint, can be found online at: www.aclu.org/brca.

Published on American Civil Liberties Union (http://www.aclu.org/)

Source URL: http://www.aclu.org/free-speech-womens-rights/patents-breast-cancer-genes-ruled-invalid-aclupubpat-case.
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China Stakes Claim as Global Centre for Scientific Research

China Stakes Claim as Global Centre for Scientific Research Thursday, 14 January 2010 Contrary to popular belief, China is doing much more than exporting clothing, toys, electronics, and other popular consumer goods. The country is on a scientific roll, to the point where it could conceivably be regarded as the emerging global centre for scientific research, a new report indicates. It describes an amazing growth in chemical patenting and publishing that could bring new and innovative products to the world market ranging from pharmaceuticals to microchips, according to an article in the current issue of Chemical & Engineering News, (C&EN) ACS' weekly newsmagazine. C&EN Senior Editor Sophie L. Rovner reports that China in 2009 became the world leader in the number of chemistry patent applications published annually. China published 67,000 patent applications in 2009, compared to 52,000 for Japan and 41,000 for the United States. Publication of scientific papers originating in China increased faster than any other nation during the last 10 years. The output of papers with Chinese authors more than quadrupled — from 20,000 papers in 1998 to more than 112,000 in 2008. The publication of U.S. scientific papers rose by barely 30 percent during that period. In achieving this growth, scientists in China are embracing collaborators in the U.S. and other countries. It is becoming increasingly clear that the country is changing the "world map of research," with China conceivably at its centre, the article suggests. This story is available at China Ascendant. ......... ZenMaster

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ACLU Sues over Patents on Breast Cancer Genes

ACLU – Myriad Genetics lawsuit will become landmark case Friday, 15 May 2009 The American Civil Liberties Union action in filing a lawsuit yesterday against Myriad Genetics is going to lead to one of the most important legal battles in the history of biotechnology, asserts Genetic Engineering & Biotechnology News (GEN). The ACLU charged that the patenting of two human genes linked to breast and ovarian cancer will inhibit medical research. The organization also claims that the patents are invalid and unconstitutional. "This is going to turn into one of the watershed events in the evolution of the bioindustry," says John Sterling, Editor in Chief of GEN. "The pros and cons of patenting genes have been an ongoing, and often acrimonious series of debates, since the in re Chakrabarty decision in 1980. But this particular case seems to have taken on a life of its own with over fifteen plaintiffs. For while the lawsuit specifically centres on the patentability of two cancer-related genes, the ACLU says it plans to challenge the entire concept of patenting genes. What we have here is one group, the ACLU and its allies, contending that gene patents stifle life science research and potentially harm the health of thousands of patients. On the other side are biotech companies who maintain that without gene patents research incentives are seriously diminished and innovation is smothered." Kenneth I. Berns, M.D., Ph.D., Editor in Chief of the peer-reviewed journal, Genetic Testing and Molecular Biomarkers, which is the official journal of the Genetic Alliance, says the "patenting of human genes is a bad idea and that healthcare in the U.S. would be enhanced if the ACLU suit prevails." Dr. Berns is also Director of the University of Florida Genetics Institute in Gainesville. William Warren, partner at the Sutherland law firm, thinks the ACLU, in this case, is barking up the wrong tree. "The ACLU unexpectedly based its invalidity challenge on claims to un-patentable subject matter," he says. "The ACLU might have instead considered challenging the Myriad patents for obviousness." Warren and Sutherland colleague, Lei Fang, Ph.D., M.D., have authored a legal article, which will be published in the June 1 issue of GEN entitled "Patentability of Genetic Sequences Limited." For the specific details surrounding the lawsuit, please see the article on the GEN website entitled "Myriad Genetics Comes under Legal Fire for Gene Patents", which includes pertinent comments from both research and legal professionals. ......... ZenMaster

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Spun-sugar Fibres Spawn Sweet Technique for Nerve Repair

Spun-sugar Fibres Spawn Sweet Technique for Nerve Repair Friday, 27 February 2009 Researchers at Purdue University have developed a technique using spun-sugar filaments to create a scaffold of tiny synthetic tubes that might serve as conduits to regenerate nerves severed in accidents or blood vessels damaged by disease. The sugar filaments are coated with a corn-based degradable polymer, and then the sugar is dissolved in water, leaving behind bundles of hollow polymer tubes that mimic those found in nerves, said Riyi Shi, an associate professor in Purdue's Weldon School of Biomedical Engineering and Department of Basic Medical Sciences. The scaffold could be used to promote nerve regeneration by acting as a bridge placed between the ends of severed nerves, said biomedical engineering doctoral student Jianming Li, who is a member of Shi's research team that developed the technique.

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Purdue researchers have developed a technique using sugar filaments spun like cotton candy and coated with a polymer to create a scaffold of tiny synthetic tubes that might serve as conduits to regenerate nerves severed in accidents or damaged by disease. The image on the left, taken with a scanning electron microscope and artificially coloured, shows the sugar strands in yellow and the polymer coating in blue. Images on the right, taken with the same instrument, show a side view of the tubes and tiny pores that are ideal for supplying nutrients to growing nerve cells and removing waste products from the cells. Credit: Weldon School of Biomedical Engineering, Department of Basic Medical Sciences and the Center for Paralysis Research, Purdue University.

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The researchers are initially concentrating on the peripheral nerves found in the limbs and throughout the body because nerve regeneration is more complex in the spinal cord. About 800,000 peripheral nerve injuries are reported annually in the United States, with about 50,000 requiring surgery. The approach also might have applications in repairing blood vessels damaged by trauma and disease such as atherosclerosis and diabetes, Shi said. The new approach represents a potential alternative to the conventional surgical treatment, which uses a nerve "autograft" taken from the leg or other part of the body to repair the injured nerves. Researchers are trying to develop artificial scaffolds to replace the autografts because removing the donor nerve causes a lack of sensation in the portion of the body where it was removed. "The autograft is the lesser of two evils because you have to sacrifice a healthy nerve to repair a damaged segment," said Li, who led the research. New findings were published online in December and this month in the print edition of the journal Langmuir. The paper was written by Li, biomedical engineering doctoral student Todd A. Rickett and Shi. Rickett also is attending the Indiana University School of Medicine in an MD-Ph.D. program. Researchers from Cornell University published similar findings online Feb. 9 in the journal Soft Matter. Those findings focused on using the technique to create vascular networks for providing blood and nutrients to tissues and grafts.

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Researchers at Purdue have developed a technique using sugar filaments spun like cotton candy and coated with a polymer to create a scaffold of tiny synthetic tubes that might serve as conduits to regenerate nerves severed in accidents or damaged by disease. These images, taken with fluorescent-dyed samples, show nerve-insulating cells called Schwann cells (on left) growing on a tubule, and a combination of Schwann cells and neurons aligned lengthwise along the tubes (on right). This alignment is critical for the fast growth of nerves. Credit: Weldon School of Biomedical Engineering, Department of Basic Medical Sciences, and the Center for Paralysis Research, Purdue University.

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The synthetic scaffold resembles the structural assembly of natural nerves, which are made of thousands of small tubes bundled together. These tubes act as sheaths that house the conducting elements of the nerve cell. The first step in making the tubes is to spin sugar fibres from melted sucrose. "It's basically like making cotton candy," Li said. The sugar filaments were coated with a polymer called poly L-lactic acid. After the filaments were dissolved, hollow tubes of the polymer remained. The researchers then grew nerve-insulating cells called Schwann cells on these polymer tubes. These cells automatically aligned lengthwise along the tubes, as did nerve cells grown on top of the Schwann cells. This alignment is critical for the fast growth of nerves, Shi said. Nerve cells grew not only inside the hollow tubes but also around the outside of the tubes. "This finding is important because the increased surface area may accelerate the regeneration process following an accident," Li said. The scaffolds are designed specifically to regenerate a portion of a nerve cell called the axon, a long fibre attached to the cell body that transmits signals. Fast regeneration is essential to prevent the atrophy of muscles and organs connected to severed nerves. The researchers also discovered that the polymer tubes contain pores that are ideal for supplying nutrients to growing nerve cells and removing waste products from the cells. Images of the polymer-coated sugar strands were taken using a scanning electron microscope. Another instrument, called an atomic force microscope, was used to obtain images of the hollow tubes and pores in the walls of the tubules. Other images using fluorescent dyes revealed the nerve cell alignment along the tubes. The work was done using cell cultures in Petri-dishes, but ongoing work focuses on implanting the scaffolds in animals. The method for creating the scaffolds is relatively simple and inexpensive and does not require elaborate laboratory equipment, Shi said. "This is low-tech," he said. "We used the same kind of sugar found in candy and a cheap polymer to make samples of these scaffolds for a few dollars. The process easily lends itself to mass production. It is a unique idea, and the simplicity and efficiency of this technology distinguish it from other approaches for nerve repair." A provisional patent application on the material has been filed. Reference: Biomimetic Nerve Scaffolds with Aligned Intraluminal Microchannels: A "Sweet" Approach to Tissue Engineering Jianming Li, Todd A. Rickett and Riyi Shi Langmuir, 2009, 25 (3), pp 1813–1817, DOI: 10.1021/la803522f ......... ZenMaster

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Tiny Sacs from Cells Carry Information about Tumours

Exosomes deliver factors that promote tumour growth and may serve as blood biomarkers Monday, 17 November 2008 Microvesicles – tiny membrane-covered sacs – released from glioblastoma cells contain molecules that may provide data that can guide treatment of the deadly brain tumour. In their report in the December 2008 Nature Cell Biology, which is receiving early online release, Massachusetts General Hospital (MGH) researchers describe finding tumour-associated RNA and proteins in membrane microvesicles called exosomes in blood samples from glioblastoma patients. Detailed analysis of exosome contents identified factors that could facilitate a tumour's growth through delivery of genetic information or proteins, or signify its vulnerability to particular medications. "Glioblastomas release exosomes in sufficient quantities to pass the blood-brain barrier. We were able to isolate them, analyze the RNA transcripts and show how they might be used as biomarkers to guide targeted therapy and monitor treatment response," says Johan Skog, PhD, the study's lead author, who works in the laboratory of Xandra Breakefield, PhD, at the MGH Neuroscience Center. "Exosomes also may someday be used to deliver therapeutic molecules to the site of a tumour," he added. Many types of cells release exosomes as part of normal cell-to-cell communication, and several types of tumours are known to shed exosomes containing proteins that can alter the cellular environment to favour tumour growth. The current investigation is believed to be the first to carefully analyze the contents of exosomes shed from glioblastoma cells and characterize their contents. The investigators first analyzed tumour cells from three glioblastomas and verified that the cells released exosomes containing RNA and protein molecules. Some messenger RNAs related to activities such as cell proliferation and migration, angiogenesis, and immune response were highly abundant in the exosomes. When glioblastoma exosomes were cultured with normal cells, tumour RNA was delivered into the normal cells and generated its encoded protein, supporting the role of exosome-delivered RNA in manipulating the cellular environment. To study the potential of glioblastoma exosomes as markers of a tumour's genetic makeup, the researchers analyzed tumour tissue and blood serum from 25 glioblastoma patients and were able both to find tumour exosomes and to identify, in some tissue samples, a mutation in the epidermal growth factor receptor (EGFR) gene that characterizes a tumour subtype. In two patients, an EGFR mutation that did not appear in the tumour tissue sample was identified by exosome analysis, reflecting how a surgical biopsy can miss tissue conveying critical information because of the often-chaotic diversity of cells within a tumour. "It is known that the effects of some anticancer drugs depend on a tumour's genetic mutational profile, so our results have broad implications for personalized medicine," explains Skog, who is an instructor in Neurology at Harvard Medical School. "Detecting mutational profiles through a non-invasive blood test could allow us to monitor how a tumour's genetic makeup changes in response to therapy, which may necessitate changes in treatment strategy." Skog, Breakefield and their colleagues are also investigating the role of exosomes in other solid tumours and how they may help monitor additional tumour-associated mutations. The current study was supported by grants from the Wenner-Gren Foundation, Stiftelsen Olle Engkvist Byggmästare, the National Cancer Institute, the Brain Tumour Society and the American Brain Tumour Association. The MGH's provisional patent on the work described in this study has been exclusively licensed to Exosome Diagnostics, Inc.. Subsequent to the completion of this work, Skog was appointed the company's director of Research, while maintaining his position at MGH. ......... ZenMaster

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Novel Method to Grow Human Embryonic Stem Cells

Uses no animal-based materials; could change how labs culture hESCs in the future Wednesday, 20 August 2008 The majority of researchers working with human embryonic stem cells (hESCs) – cells which produce any type of specialized adult cells in the human body – use animal-based materials for culturing the cells. But because these materials are animal-based, they could transmit viruses and other pathogens to the hESCs, making the cells unsuitable for medical use. Now, a stem-cell scientist at UC Riverside has devised a method of growing hESCs in the lab that uses no animal-derived materials – an important advance in the use of hESCs for future medical purposes. Because of their tremendous potential, hESCs are considered promising sources for future cell therapy to treat diseases such as Parkinson's disease and diabetes mellitus. Noboru Sato, an assistant professor of biochemistry, developed the new method, which is not only cleaner and easier to use than conventional methods of culturing hESCs but also results in hESCs whose pluripotency – the potential to differentiate into any of the specialized cells of the body such as neurons, cardiac muscles, and insulin-producing cells – is uncompromised. Currently in labs worldwide, many researchers grow hESCs on Matrigel-coated culture plates, Matrigel being the trade name for a gelatinous extract, taken from mouse tumour cells, that contains extracellular matrices (ECMs), made up of special proteins. The Matrigel coating provides the scaffolding to which the hESCs first attach and then grow in undifferentiated colonies before differentiating into specialized cells.

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Caption: hESCs grown on Matrigel in defined culture media. The mesh-like structure in the background is Matrigel. Credit: Sato lab, UC Riverside

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"The development of animal-free coating methods for hESCs still remains a major challenge due to the complexity of ECMs and insufficient knowledge about how hESCs control cell-cell and cell-ECM interactions," explained Sato, who led the research project. His lab identified a specific signalling pathway, called Rho-Rock, which the hESCs use during colony formation and which plays an important role in physical interactions between hESCs. When the researchers blocked the pathway, they found, as expected, that the normal colony formation of hESCs was considerably impaired. They also found that the hESCs maintained their pluripotency. "Until now, it was generally assumed that the hESC colony formation was pivotal for maintaining pluripotency," Sato said. "But we show that pluripotency can be retained independent of close cell-cell contact."

Prue Talbot, the director of UCR's Stem Cell Center

of which Sato is a member, noted that Sato's discovery could affect the way embryonic stem cells are grown in the future. "His work is certainly an important step forward in both understanding signal transduction pathways in stem cells and in the development of an improved methodology for culturing stem cells," she said. In the study, Sato's group extensively screened various types of scaffold materials in combination with Y27632, a chemical compound that blocks the Rho-Rock pathway, and found that the Matrigel coating could be replaced with "poly-D-lysine," a chemically synthesized ECM. The major advantages of poly-D-lysine over Matrigel are that poly-D-lysine is completely animal-free, easy to handle, and its quality is consistent.

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Caption: hESCs grown on poly-D-lysine-coated plate in defined culture media with Y27632. Credit: Sato lab, UC Riverside.

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"We found that the growth of the hESCs under this novel culture condition was almost identical to the growth of hESCs on Matrigel-coated culture plates, with no compromise in pluripotency," Sato said. Having started his career as a physician in Japan, Sato began researching stem cell biology as a research fellow at The Rockefeller University, NY, one of the foremost research centres in the world. He accepted a faculty position in the Department of Biochemistry at UCR in 2006. Nicole Harb of UCR and Trevor K. Archer of the National Institute of Environmental Health Sciences (NIEHS), NC joined him in the research project. The research was a collaboration between UCR and NIEHS, and funded by UCR start-up funds to Sato and a grant to Archer from the National Institutes of Health. "Our research goal is to understand the basic mechanisms underlying unique biological functions of pluripotent stem cells, and to translate the obtained knowledge into future medical applications," Sato said. His group is now focusing on applying his technique to the latest stem cell technology, "induced pluripotent stem (iPS) cells," which are pluripotent stem cells artificially derived from adult cells without using embryos. "Our next step is to produce new animal-free iPS cell lines," Sato said. UCR's Office of Technology Commercialization has applied for a patent on Sato's discovery and is looking for industrial partners interested in further developing it. Reference: The Rho-Rock-Myosin Signaling Axis Determines Cell-Cell Integrity of Self-Renewing Pluripotent Stem Cells Nicole Harb, Trevor K. Archer, Noboru Sato PLoS ONE (2008), 3(8): e3001. doi:10.1371/journal.pone.0003001 ......... ZenMaster

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For Sale: Bodies, Parts, Eggs, Genes, Stem Cells

For sale: Bodies, parts, eggs, genes, stem cells Monday, 04 August 2008 Author: Donna Dickenson In the 1960s, feminists coined the slogan, "Our bodies, our selves." But that liberating sentiment has recently undergone an ironic twist. As an anonymous American woman, justifying her decision to undergo cosmetic surgery, put it, "All we have in life is ourselves, and what we can put out there every day for the world to see ... Me is all I got." The French commentator Herve Juvin extolled this new attitude towards the body in his 2005 surprise bestseller, "Lavenement du Corps" ("The Coming of the Body"). Plastic surgery, the implantation of biochips, piercings — all emblazon the belief that our bodies are our unique property. At the same time, Juvin asserts, because everyone has a body, property has suddenly become democratized. We appear to live in a time that has witnessed the absolute failure of the grand Enlightenment dreams of linear progress, universal peace, and equality between rich and poor. Together with widespread hostility to organized religion, manifested in such hugely popular books as Richard Dawkins's "The God Delusion," disappointment with social ideals means that we turn inward. In the absence of a belief in eternal life, everything becomes invested in this life, this body. Long life is our desire, eternal youth our supposed right, and the myth of the body without origin or limits our new religion. That might be why governments are so widely seen to have a positive duty to promote stem cell research and other forms of medical progress. Biotechnology industries flourish, with state sanction and support, because they add extra value to the body, the object of supreme worth to us. Indeed, the infinite renewal of the body isn't confined to superficial repairs through cosmetic surgery. External substitutes for organic structures can be surgically implanted, breaking down the barrier between the body and the outside world. At the same time, tissue removed from the body enters into commerce and trade as a commodity like any other, in the form of stem cell lines, human eggs, and other "products." The American law professor James Boyle believes that we can grasp the way in which the body has become an object of trade by likening it to the historical process of enclosure. In 18th-century Britain, land, which was previously a public resource, was "enclosed" by private owners. Freed of feudal-style legal restrictions on transfer of ownership and of traditional rights held by commoners who used communal land to pasture their animals, landholdings could now be sold to raise capital, which helped to finance the industrial revolution. In modern biotechnology, Boyle thinks, things previously outside the market — once thought to be impossible to commodify — are becoming routinely privatized. One in five human genes is now patented, even though the human genome might be thought to be our common heritage. And although Boyle doesn't mention this latest development, umbilical cord blood, taken in the final stage of labour, is now banked by profit-making firms as a potential — though unlikely — source of stem cells for the baby. In biomedicine, a series of legal cases have generated powerful momentum toward the transfer of rights over the body and its component parts from the individual "owner" to corporations and research institutions. So the body has entered the market, becoming capital, just as land did, though not everyone benefits, any more than the dispossessed commoners grew wealthy during the agricultural enclosures. Most people are shocked when they learn that one-fifth of the human genome has been patented, mostly by private firms. But why be so surprised? After all, female bodies have been subject to various forms of property-holding over many centuries and in many societies. Women's bodies are used to sell everything from cars to pop music, of course. But female tissue has been objectified and commodified in much more profound ways, in legal systems from Athens onwards. While men were also made into objects of ownership and trade, as slaves, in general women were much more likely to be treated as commodities in non-slave-owning systems. Once a woman had given her initial consent to the marriage "contract," she had no right to retract her consent to sexual relations — ever. There are clear parallels between that situation and the way in which the common law has offered little redress to patients who have tried to claim property rights in tissue taken from them. About the source: The author, Donna Dickenson, is Emeritus professor of Medical Ethics and Humanities at the University of London, was the 2006 winner of the International Spinoza Lens Award for contribution to public debate on ethics. Copyright: Project Syndicate/Institute for Human Sciences, 2008. www.project-syndicate.org ......... ZenMaster

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To Good To Be True?

Paralyzed man back on his feet after embryonic stem cell therapy Monday, 28 April 2008 The Grand Junction Sentinel in Colorado today report about a man receiving embryonic stem cell treatment in India, after a spinal cord accident several years ago. In December, he went to Dr. Geeta Shroff’s clinic at the Nu Tech Mediworld medical center in New Delhi. She is originally an infertility expert, that say’s she have developed the embryonic stem cell therapy offered there. For the next two months, Rusty Leech received stem cell therapy in several ways: twice-daily injections into his upper arms, three weeks of intravenous stem cell fluids, and five large injections near his spinal cord at the point of his initial injury — the thoracic 10 vertebrae. The treatment also included intense and daily physical therapy designed to help rebuild the muscles that atrophied during the many years of paralysis. He was never told how many stem cells he received, and he doesn’t know exactly how and why Shroff’s treatments work. Shroff’s treatment has been much criticised and questioned, because she has never publicized any details of her procedures. The reason for this, she maintain, is that she is seeking a patent for her therapy in many countries across the globe, including the United States. Is this a miracle cure, or is the improvements seen by Rusty coming from the intense physical therapy only? No-one can really say, before detailed scrutiny of the procedure is disclosed. That this happens, not only at this clinic in New Delhi but at several other locations around the world, is very unfortunate for the medical world, and especially for all suffering patients waiting for some new procedures to alleviate their sufferings. All scientists and medical researchers should, as soon as possible, describe their results in detail, so that the effectiveness can be assessed by others too. It is not moral to wait for patents or any other monetary benefits. Read more at: 'Unbelievable': Paralyzed man back on his feet after embryonic stem cell therapy Grand Junction Sentinel, CO, Monday, April 28, 2008 Watch a Video of Rusty. ......... ZenMaster

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The Latest About Synthetic Life

Read The Latest About Synthetic Life Synthetic DNA on the Brink of Yielding New Life Forms Washington Post - Monday, December 17, 2007 ......... ZenMaster For more on stem cells and cloning, go to CellNEWS at http://www.geocities.com/giantfideli/index.html

Next Step Towards Artificial Life

Whole Genome Transplantation Achieved in Mycobacteria June 28, 2007 Researchers at the J. Craig Venter Institute (JCVI) today 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, published online in the journal Science, by JCVI’s Carole Lartigue, Ph.D. and colleagues, outlines 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. “The successful completion of this research is important because it is one of the key proof of principles in synthetic genomics that will allow us to realize the ultimate goal of creating a synthetic organism,” said J. Craig Venter, Ph.D., president and chairman, JCVI. “We are committed to this research as we believe that synthetic genomics holds great promise in helping to solve issues like climate change and in developing new sources of energy.” Methods and techniques The JCVI team devised several key steps to enable the genome transplantation. First, an antibiotic selectable marker gene was added to the M. mycoides LC chromosome to allow for selection of living cells containing the transplanted chromosome. Then the team purified the DNA or chromosome from M. mycoides LC so that it was free from proteins (called naked DNA). This M. mycoides LC chromosome was then transplanted into the M. capricolum cells. After several rounds of cell division, the recipient M. capricolum chromosome disappeared having been replaced by the donor M. mycoides LC chromosome, and the M. capricolum cells took on all the phenotypic characteristics of M. mycoides LC cells. As a test of the success of the genome transplantation, the team used two methods — 2D gel electrophoresis and protein sequencing, to prove that all the expressed proteins were now the ones coded for by the M. mycoides LC chromosome. Two sets of antibodies that bound specifically to cell surface proteins from each cell were reacted with transplant cells, to demonstrate that the membrane proteins switch to those dictated by the transplanted chromosome not the recipient cell chromosome. The new, transformed organisms show up as bright blue colonies in images of blots probed with M. mycoides LC specific antibody. The group chose to work with these species of mycoplasmas for several reasons — the small genomes of these organisms which make them easier to work with, their lack of cell walls, and the team’s experience and expertise with mycoplasmas. The mycoplasmas used in the transplantation experiment are also relatively fast growing, allowing the team to ascertain success of the transplantation sooner than with other species of mycoplasmas. According to Dr. Lartigue, “While we are excited by the results of our research, we are continuing to perfect and refine our techniques and methods as we move to the next phases and prepare to develop a fully synthetic chromosome.”Genome transplantation is an 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. The ability to transfer the naked DNA isolated from one species into a second microbial species paves the way for next experiments to transplant a fully synthetic bacterial chromosome into a living organism and if successful, “boot up” the new entity. There are many important applications of synthetic genomics research including development of new energy sources and as means to produce pharmaceuticals, chemicals or textiles. Background and Ethical Considerations The work described by Lartigue et al. has its genesis in research begun by Dr. Venter and colleagues in the mid-1990’s after sequencing Mycoplasma genitalium and beginning work on the minimal genome project. This area of research, trying to understand the minimal genetic components necessary to sustain life, 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. 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.Dr. Venter and the team at JCVI continue to be concerned with the societal implications of their work and the field of synthetic genomics generally. As such, the Institute’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 15-month study to explore 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 is set to publish a report in summer 2007 outlining options for the field and its researchers. About the J. Craig Venter Institute The J. Craig Venter Institute 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 500 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. For additional information, please visit http://www.jcvi.org/. Genome Transplantation in Bacteria - Science, 29/06/2007 Also read: Venter Attempt a Minimalistic Approach of Creating ‘Artificial’ Life ......... ZenMaster

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Synthetic Biology

Scientists call for global push to advance research in synthetic biology June 25, 2007 With research backgrounds ranging from materials engineering to molecular biophysics, seventeen leading scientists issued a statement today announcing that, much as the discovery of DNA and creation of the transistor revolutionized science, there is a new scientific field on the brink of revolutionizing our approach to problems ranging from eco-safe energy to outbreaks of malaria: synthetic biology. ......... ZenMaster

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Biologics Rapidly Becoming New Frontier in Drug Arena

Biologics Rapidly Becoming New Frontier in Drug Arena, FDLJ Article Concludes Monday, 18 June 2007 Dolly was cloned only adecade ago. Since then, there's been an almost cataclysmic revolution in our understanding of biologics, with potentially significant implications for every facet of the health care delivery system in the United States. This awareness of new types of biologics, which now range from universal vaccines for possibly curing cancer, to genetically engineered plants and animals that produce biologics for human or veterinary use, is raising thorny issues for agency regulators, Congressional lawmakers and biotech representatives, such as:

• How should FDA and Congress define biologics as part of new legislation under consideration that will allow the marketing of "generic"or "follow on" versions and does it really matter?
• Do we need a whole new statutory or regulatory scheme for defining human and veterinary biologics?
• How or why do cells, tissues and cloning qualify as biologics?
• What's the best way to define biologics to accommodate rapid and complex technological advances in the development of new medicines?

In the current issue of the Food and Drug Law Journal (Vol. 62, No. 2), published by the Food and Drug Law Institute, attorney and scientist Edward L. Korwek helps policymakers address these and other issues by offering the most comprehensive, historical analysis to date of the major changes in the statutory and regulatory definitions of human and veterinary biologics in the last 100 years. The FDLJ article analyzes and compares in-depth the criteria for human and veterinary biological product status related to the treatment of infectious diseases, gene and cell therapies, tissue engineering and cloning, among other products of both new and older technologies. Korwek, a senior partner with the law firm of Hogan & Hartson, LLP, in Washington, D.C., notes that while the "regulatory recipes" for human and animal biologics differ in several key aspects, neither covers two critical areas in the drug arena: antibiotics and hormones. The bottom line,according to the article: Regulating innovative technical applications of human and other animal medicines as biologics has become one of the most important challenges facing the drug industry today. .........

ZenMaster

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Stem cell patent might go

3 Patents on Stem Cells Are Revoked in Initial Review New York Times, NY - 20070403 The United States Patent and Trademark Office has made a preliminary decision to revoke three fundamental patents on human embryonic stem cells. If the decision stands, some scientists and consumer groups say it could loosen restrictions on research in a promising new field. ........... ZenMaster