StemCell Therapy

Public release date: 26-Jul-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, July 26, 2012 Administering high-doses of interleukin-2 (IL-2) has been the preferred treatment for patients with stage IV metastatic melanoma. An article published in the current issue of Cancer Biotherapy and Radiopharmaceuticals, a peer-reviewed journal from Mary Ann Liebert, Inc. (http://www.liebertpub.com), explores whether or not this regimen is still the most effective. The article is available free online at the Cancer Biotherapy and Radiopharmaceuticals website (http://www.liebertpub.com/cbr).

In the article "Should High-Dose Interleukin-2 Still Be the Preferred Treatment for Patients with Metastatic Melanoma?" (http://online.liebertpub.com/doi/full/10.1089/cbr.2012.1220) Robert Dillman and colleagues at the Hoag Institute for Research and Education and Hoag Family Cancer Institute, Newport Beach, CA concluded that until long-term survival data for some of the newer drugs are available, patients with stage IV metastatic melanoma who are well enough to be given intensive IL-2 therapy should receive it initially, either alone or in combination with one of the newer therapeutic agents.

"This is an important article that puts into perspective the reasons why IL-2 should continue to be the initial therapy in patients with metastatic melanoma," says Editor Donald J. Buchsbaum, PhD, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama at Birmingham.

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About the Journal

Cancer Biotherapy and Radiopharmaceuticals (http://www.liebertpub.com/cbr), published 10 times a year in print and online, is under the editorial leadership of Editors Donald J. Buchsbaum, PhD and Robert K. Oldham, MD, Lower Keys Cancer Center, Key West, FL. Cancer Biotherapy and Radiopharmaceuticals is the only journal with a specific focus on cancer biotherapy, including monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapy. The Journal includes extensive reporting on advancements in radioimmunotherapy and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments. Topics include antibody drug conjugates, fusion toxins and immunotoxins, nanoparticle therapy, vascular therapy, and inhibitors of proliferation signaling pathways.

About the Publisher

Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com) is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Journal of Interferon & Cytokine Research, Human Gene Therapy and Human Gene Therapy Methods, and Stem Cells and Development. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available at Mary Ann Liebert, Inc. (http://www.liebertpub.com)

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Should high-dose interleukin-2 continue to be the treatment of choice for metastatic melanoma?

Public release date: 24-Jul-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, July 24, 2012A naturally occurring line of immunodeficient pigs can support the growth of human tumors injected under their skin, offering a promising new large animal model for studying human cancers and testing new drugs and treatment strategies. The ability of human melanoma cells and pancreatic carcinoma cells to grow in these pig models is described in an article in BioResearch Open Access, a new bimonthly peer-reviewed open access journal from Mary Ann Liebert, Inc. (http://www.liebertpub.com). The article is available free online at the BioResearch Open Access website (http://www.liebertpub.com/biores).

Mathew Basel and colleagues, Kansas State University (Manhattan, KS) and Iowa State University (Ames), highlight the advantages that pig disease models offer, as they are anatomically and physiologically more closely related to humans than traditional rodent animal models. As a result, findings from studies in large animal models such as pigs are more likely to translate into similar outcomes in humans. The authors present their findings in the article "Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs" (http://online.liebertpub.com/doi/full/10.1089/biores.2012.9902).

"This novel animal model has the potential to become a highly useful model in cancer research studies, in addition to providing significant opportunities for drug discovery and other translational applications," says Editor-in-Chief Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

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About the Journal

BioResearch Open Access (http://www.liebertpub.com/biores) is a bimonthly peer-reviewed open access journal that provides a new rapid-publication forum for a broad range of scientific topics including molecular and cellular biology, tissue engineering and biomaterials, bioengineering, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. All articles are published within 4 weeks of acceptance and are fully open access and posted on PubMedCentral. All journal content is available online at the BioResearch Open Access website (http://www.liebertpub.com/biores).

About the Publisher

Mary Ann Liebert, Inc., publishers (http://www.liebertpub.com) is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, Human Gene Therapy and HGT Methods, and AIDS Research and Human Retroviruses. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc. website (http://www.liebertpub.com).

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Novel pig model may be useful for human cancer studies

Public release date: 17-Jul-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, July 16, 2012A small, naturally occurring nucleic acid sequence, called a microRNA, known to regulate a number of different cancers, appears to alter the activity of the androgen receptor, which plays a critical role in prostate cancer. Directly targeting microRNA-125b to block androgen receptor activity represents a novel approach for treating castrate-resistant prostate cancer. This promising new strategy for improving the effectiveness of anti-androgenic and other hormonal therapies is described in an article in BioResearch Open Access, a new bimonthly peer-reviewed open access journal from Mary Ann Liebert, Inc.. The article is available free online at the BioResearch Open Access website.

Prostate cancer is the most common non-skin cancer affecting men and the second most common cause of cancer death among men. In the article "miR-125b Regulation of Androgen Receptor Signaling Via Modulation of the Receptor Complex Co-Repressor NCOR2," Xiaoping Yang, Lynne Bernis, Lih-Jen Su, Dexiang Gao, and Thomas Flaig, University of Colorado Denver (Aurora) and University of Minnesota (Duluth), looked for targets of microRNA-125b that might shed light on its role in regulating prostate cancer and found that it directly inhibits NCOR2, which acts to repress the androgen receptor. The authors point out that "the androgen receptor is a critical therapeutic target in prostate cancer" and that alterations in the receptor are essential for the development of castrate-resistant prostate cancer, in which the disease no longer responds to hormonal therapies.

"This research provides new insight into the mechanism of miR-125b regulation of castrate-resistance prostate cancer through the identification of a novel target for miR-125b," says Editor-in-Chief Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland. "The clinical implications of this study are that targeted regulation of this miRNA may lead to more effective anticancer therapies."

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About the Journal

BioResearch Open Access is a bimonthly peer-reviewed open access journal that provides a new rapid-publication forum for a broad range of scientific topics including molecular and cellular biology, tissue engineering and biomaterials, bioengineering, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. All articles are published within 4 weeks of acceptance and are fully open access and posted on PubMedCentral. All journal content is available online at the BioResearch Open Access website.

About the Publisher

Mary Ann Liebert, Inc., is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, Human Gene Therapy and HGT Methods, and AIDS Research and Human Retroviruses. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc. website.

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New therapeutic target for prostate cancer identified

Public release date: 10-Jul-2012 [ | E-mail | Share ]

Contact: John Sterling jsterling@genengnews.com 914-740-2196 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, July 9, 2012More than half (52%) of the companies comprising the tissue engineering (TE) and stem cell industries are revenue-generating, compared to about 21% four years ago, reports Genetic Engineering & Biotechnology News (GEN). Of those companies, 31% have commercial products and 21% are service-based; another 30% have products in clinical trials, according to the current issue of GEN.

The GEN article is based on interviews with leading tissue engineering researchers and on the findings of a landmark paper ("Progress in the Tissue Engineering and Stem Cell Industry, Are we there yet"), which appears in Tissue Engineering: Part B, Volume 18, Number 3, 2012, published by Mary Ann Liebert, Inc.

"Like many other biotechnologies, tissue engineering has experienced an up and down history," said John Sterling, Editor in Chief of GEN. "But with numerous technical advances moving the field forward combined now with rising revenues, this segment of bioresearch is really taking off."

The industry itself is beginning to attain profitability, with sales revenues reaching $3.5 billion and industry spending approaching $3.6 billion. The 2012 analysis by a group led by Robert Langer, Sc.D., one of the authors of the paper in the Liebert journal, reported a nearly threefold increase in commercial sales for TE and stem cell products and services compared to the previous four-year period. Furthermore, the number of companies selling products or offering services increased more than twofold to 106.

The GEN article also notes that Tissue Engineering has formed an industry council for the purpose of helping to guide the evolution of the industry and to create strategic initiatives aimed at overcoming some of the R&D, manufacturing, and regulatory challenges facing the industry.

Among the companies interviewed for the GEN article are Organogenesis, Cytograft Tissue Engineering, Scintellix, and Humacyte.

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For a copy of the July issue of GEN, please call (914) 740-2146, or email: pbartell@genengnews.com

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GEN reports on growth of tissue engineering revenues

MADISON, Wis., June 7, 2012 /PRNewswire/ --Cellular Dynamics International, Inc. (CDI), the world's largest commercial producer of human induced pluripotent stem (iPS) cell lines and tissue cells, today announced the launch of its MyCell Services. These services include novel iPS cell line reprogramming, genetic engineering and differentiation of iPS cells into commercially available iCell terminal tissue cells (for example, heart or nerve cells).

"CDI's mission is to be the top developer and manufacturer of standardized human cells in high quantity, quality and purity and to make these cells widely available to the research community. Our MyCell Services provide researchers with unprecedented access to the full diversity of human cellular biology," said Bob Palay, CDI Chief Executive Officer. "The launch of MyCell Services furthers CDI founder and stem cell pioneer Jamie Thomson's vision to enable scientists worldwide to easily access the power of iPSC technology, thus driving breakthroughs in human health."

Over the past 2 years, CDI has launched iCell Cardiomyocytes, iCell Neurons and iCell Endothelial Cells for human biology and drug discovery research. MyCell Services leverage CDI's prior investment in building an industrial manufacturing platform that can handle the parallel production of multiple iPSC lines and tissue cells, manufacturing billions of cells daily.

Chris Parker, CDI Chief Commercial Officer, commented, "Not all studies requiring human cells can be accomplished by using cells from a limited set of normal, healthy donors. Researchers may need iPS cells or tissue cells derived from specific ethnic or disease populations, and MyCell Services enable them to take advantage of our deep stem cell expertise and robust industrial manufacturing pipeline to do so. Previously, scientists had to create and differentiate iPS cells themselves. Such activities consume significant laboratory time and resources, both of which could be better applied to conducting experiments that help us better understand human biology. CDI's MyCell Services enable scientists to re-direct those resources back to their experiments."

CDI pioneered the technique to create iPS cells from small amounts of peripheral blood, although iPS cells can be created from other tissue types as well. Additionally, CDI's episomal reprogramming method is "footprint-free," meaning no foreign DNA is integrated into the genome of the reprogrammed cells, alleviating safety concerns over the possible use of iPS cells in therapeutic settings. These techniques have been optimized for manufacture of over 2 billion human iPS cells a day, and differentiated cells at commercial scale with high quality and purity to match the research needs.

Modeling Genetic Diversity

CDI has several projects already underway using MyCell Services to model genetic diversity of human biology. The Medical College of Wisconsin and CDI received a $6.3M research grant from the National Heart, Lung, and Blood Institute (NHLBI), announced July 2011, for which CDI's MyCell Services will reprogram an unprecedented 250 iPS cell lines from blood samples collected from Caucasian and African-American families in the Hypertension Genetic Epidemiology Network (HyperGEN) study. In addition, MyCell Services will differentiate these iPS cells into heart cells to investigate the genetic mechanisms underlying Left Ventricular Hypertrophy, an increase of the size and weight of the heart that is a major risk factor for heart disease and heart failure.

Researchers are also using CDI's MyCell Services to generate iPS cells and liver cells from individuals with drug induced liver injury (DILI), toward an eventual goal of identifying genetic factors linked to idiosyncratic liver toxicity. "The most problematic adverse drug event is sudden and severe liver toxicity that may occur in less than one in one thousand patients treated with a new drug, and thus may not become evident until the drug is marketed. This type of liver toxicity is not predicted well by usual preclinical testing, including screening in liver cultures derived from random human donors," said Paul B. Watkins, M.D., director of with The Hamner - University of North Carolina Institute for Drug Safety Sciences. "The ability to use iPS cell technology to prepare liver cultures from patients who have actually experienced drug-induced liver injury, and for whom we have extensive genetic information, represents a potential revolution in understanding and predicting this liability."

Screening Human Disease

While most diseases are multi-systemic, focus typically centers on only one organ system. For example, congenital muscular dystrophy (CMD) is a group of rare genetic diseases with a focus on skeletal muscle, yet other systems, including heart, eye, brain, diaphragm and skin, can be involved. Understanding the molecular mechanisms underlying complex disease phenotypes requires access to multiple tissue types from a single patient. While some systems are readily accessible for taking a biopsy sample, for example skin, other organs are not.

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Cellular Dynamics Launches MyCell™ Services

Public release date: 16-May-2012 [ | E-mail | Share ]

Contact: Cathia Falvey cfalvey@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, May 16, 2012The inaugural issue of BioResearch Open Access, a new bimonthly peer-reviewed open access journal, was released today by Mary Ann Liebert, Inc., publishers. The Journal provides a new rapid-publication forum for a broad range of scientific topics including but not limited to molecular and cellular biology, tissue engineering and biomaterials, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. The first issue is available on the BioResearch Open Access website at http://www.liebertpub.com/biores.

The premier issue includes research papers and a brief report from the U.S., U.K., Germany, and Korea on diverse topics such as tissue engineering, stem cells, HIV, and genetics. Forthcoming papers for the second issue include genetics, xenotransplantation, nuclear transfer, and cardiac research.

The Journal is under the leadership of Editor-in-Chief Jane Taylor, PhD, Senior Research Fellow, MRC Centre for Regenerative Medicine, University of Edinburgh, and seasoned journal editors as Section Editors, including James M. Wilson, MD, PhD, University of Pennsylvania; Antonios G. Mikos, PhD, Rice University; Professor Sir Ian Wilmut, OBE FRS FRSE, University of Edinburgh; Peter C. Johnson, MD, Scintellix, LLC, Raleigh, NC; Aubrey D.N.J. de Grey, PhD, SENS Foundation, Cambridge, UK; Alan J. Russell, PhD, Carnegie Mellon University; Thomas Hope, PhD, Northwestern University; Ganes C. Sen, PhD, Cleveland Clinic Foundation; Bruce A. Sullenger, PhD, Duke University Medical Center; Graham C. Parker, PhD, Wayne State University School of Medicine; Carol Shoshkes Reiss, PhD, New York University; Stephen C. Ekker, PhD, Mayo Clinic, Rochester, MN; John B. West, MD, PhD, University of California, San Diego; David L. Woodland, PhD, Chief Scientific Officer, Keystone Symposia on Molecular and Cellular Biology; Stephen Higgs, PhD, Kansas State University; Eugene Kolker, PhD, Seattle Children's Hospital; and Domenico Grasso, PhD, PE, DEE, University of Vermont.

The Journal welcomes basic science and translational research in the form of original research articles, comprehensive review articles, mini-reviews, rapid communications, brief reports, technical reports, hypothesis articles, perspectives, and letters to the editor. All articles in BioResearch Open Access will be published online within 4 weeks of acceptance. Articles will be fully open access and posted on PubMedCentral. All articles submitted through July 15, 2012 will be made open access without article processing charges. BioResearch Open Access is fully NIH-, HHMI-, and Wellcome Trust compliant.

"BioResearch Open Access is a fully refereed multidisciplinary journal and provides all the checks and balances that rigorous peer review ensures," says Mary Ann Liebert, president of Mary Ann Liebert, Inc., publishers. "An outstanding editorial team comprised of experienced journal editors guarantees the integrity of the Journal."

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About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Human Gene Therapy, Nucleic Acid Therapeutics, Stem Cells and Development, Viral Immunology, DNA and Cell Biology, and Antioxidants & Redox Signaling. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc. website at http://www.liebertpub.com.

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Premier issue of BioResearch Open Access launched by Mary Ann Liebert Inc. publishers

Devangshu Datta: Towards an HIV cure Advances in genetic engineering techniques may finally help us win the battle against this global scourge Devangshu Datta / New Delhi May 04, 2012, 00:53 IST

Since AIDS, or acquired immune deficiency syndrome, was identified in 1981, there has been only one medically-certified cure. That occurred under unusual circumstances and it gave researchers an important clue about new ways to attack the disease. Recent advances in genetic engineering techniques have aided in this process. Some studies offer new hope of a cure for the 35 million estimated to be infected worldwide.

No disease inspires as much superstitious dread. So far, AIDS is estimated to have killed over 30 million people and it infects millions every year. It is especially prevalent in Sub-Saharan Africa.

HIV is transmitted through the exchange of body fluids. Common causes of infection (not necessarily in order) include unprotected sex, blood transfusions, sharing needles and so on. The associations with promiscuity and drug addiction make it hard to implement policies to stop HIV-spread. What works best is a combination of sex education and drug awareness programmes, coupled with easy availability of condoms and disposable needles. But in conservative societies like India, people object to sex education. Some religions also discourage the use of condoms.

Someone infected with HIV (HIV-positive) may survive years, without symptoms. The virus attacks a class of white blood cells called CD4 T-cells. It inserts itself into the cell and replicates. T-cells are part of the natural immune system. Once AIDS develops owing to HIV taking over T-cells, the immune system shuts down. Most AIDS patients die of cancer, pneumonia, or some other infection.

The new approaches involve inserting immune genes into HIV-positive patients, through genetic engineering of stem cells. Every researcher is cautious about claims of cures. The characteristic long symptom-less periods and HIVs ability to hide can be cruelly deceptive. HIV-positive people are also vulnerable to quacks. Many charlatans, including a cross-dresser who teaches yoga on Indian television, have claimed at various times to have found AIDS cures.

Some people have natural genetic immunity for various reasons. Advances in understanding of genomes have helped identify some of the causes of immunity. Researchers have known for a while that a mutated gene called CCR5 Delta 32 offers natural immunity to HIV.

The mutation is rare and found only in a few northern Europeans. The normal CCR5 gene, which most people possess, is the receptor HIV uses to enter T-cells. HIV cannot use the Delta-32 mutated gene and, hence, cannot replicate in a host who has two copies of the CCR5 Delta 32 gene (one inherited from each parent). Even one copy of Delta 32 seems to offer some protection. Only about one per cent of northern Europeans possess both copies.

In 2007, Timothy Ray Brown, an American resident in Berlin, was HIV-positive and also under treatment for leukaemia. Leukaemia causes an abnormal increase in white blood cells and a drop in red cells. Blood cells are produced by bone marrow. One drastic treatment is a bone marrow stem cell transplant from a healthy person. This helps regenerate healthy blood with a good haemoglobin ratio, and a new immune system. Its dangerous since the patients entire immune system must be destroyed prior to the transplant.

Browns doctors at the Charite University Medicine Berlin, Kristina Allers and Gero Hutter, found a compatible donor who belonged to that rare one per cent with the Delta-32 mutation. Five years later, after the transplant procedures, the Berlin Patient, as Brown is called in medical journals, is still HIV-free and doctors concur that this is a functional cure.

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Devangshu Datta: Towards an HIV cure

--Study lends support to safe use for therapy

Newswise A team of researchers from Johns Hopkins University and the National Human Genome Research Institute has evaluated the whole genomic sequence of stem cells derived from human bone marrow cellsso-called induced pluripotent stem (iPS) cellsand found that relatively few genetic changes occur during stem cell conversion by an improved method. The findings, reported in the March issue of Cell Stem Cell, the official journal of the International Society for Stem Cell Research (ISSCR), will be presented at the annual ISSCR meeting in June.

Our results show that human iPS cells accrue genetic changes at about the same rate as any replicating cells, which we dont feel is a cause for concern, says Linzhao Cheng, Ph.D., a professor of medicine and oncology, and a member of the Johns Hopkins Institute for Cell Engineering.

Each time a cell divides, it has the chance to make errors and incorporate new genetic changes in its DNA, Cheng explains. Some genetic changes can be harmless, but others can lead to changes in cell behavior that may lead to disease and, in the worst case, to cancer.

In the new study, the researchers showed that iPS cells derived from adult bone marrow cells contain random genetic changes that do not specifically predispose the cells to form cancer.

Little research was done previously to determine the number of DNA changes in stem cells, but because whole genome sequencing is getting faster and cheaper, we can now more easily assess the genetic stability of these cells derived by various methods and from different tissues, Cheng says. Last year, a study published in Nature suggested higher than expected cancer gene mutation rates in iPS cells created from skin samples, which, according to Cheng, raised great concerns to many in the field pertaining to usefulness and safety of the cells. This study analyzed both viral and the improved, nonviral methods to turn on stem cell genes making the iPS cells

To more thoroughly evaluate the number of genetic changes in iPS cells created by the improved, non-viral method, Chengs team first converted human blood-forming cells or their support cells, so-called marrow stromal cells (MSCs) in adult bone marrow into iPS cells by turning on specific genes and giving them special nutrients. The researchers isolated DNA from--and sequenced--the genome of each type of iPS cells, in comparison with the original cells from which the iPS cells were derived.

Cheng says they then counted the number of small DNA differences in each cell line compared to the original bone marrow cells. A range of 1,000 to 1,800 changes in the nucleic acid letters A, C, T and G occurred across each genome, but only a few changes were found in actual genes--DNA sequences that act as blueprints for our bodys proteins. Such genes make up two percent of the genome.

The blood-derived iPS cells contained six and the MSC-derived iPS cells contained 12 DNA letter changes in genes, which led the researchers to conclude that DNA changes in iPS cells are far more likely to occur in the spaces between genes, not in the genes themselves.

Next, the investigators examined the severity of the DNA changes--how likely each one would disrupt the function of each gene. They found that about half of the DNA changes were silent, meaning these altered blueprints wouldnt change the nucleic acid building code for its corresponding protein or change its function.

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Improved Adult-Derived Human Stem Cells Have Fewer Genetic Changes Than Expected

St. Louis /PRNewswire/ -- Sigma-Aldrich Corporation (Nasdaq: SIAL) today announced that Sigma Advanced Genetic Engineering (SAGE) Labs, an initiative of Sigma Life Science, extended CompoZr Zinc Finger Nuclease (ZFN) technology to achieve the first tissue-specific conditional knockout of an endogenous gene in rats. For two decades this approach for generating sophisticated disease models could be performed only in mice. Rats, however, are preferred by drug discovery and basic researchers because the animal's physiology, neurobiology and other features are more predictive of human conditions. Rats engineered to contain tissue-specific conditional gene knockouts are available exclusively through the SAGEspeed Custom Model Development Service. Details are available at http://www.sageresearchmodels.com/conditional-KO.

Conventional gene knockout eliminates a gene throughout an entire animal. In contrast, conditional gene knockout can eliminate a gene solely in the relevant tissue or organ, leading to a more accurate understanding of the gene's function. Conditional gene knockout can also knock out genes at certain points in development, enabling studies of genes whose absence in embryos is lethal, but whose loss of function in adulthood is critical to investigate for many human diseases.

"Almost 89% of drug candidates fail to achieve approval," said Edward Weinstein, Director of SAGE Labs. "Basic and drug discovery researchers need access to more predictive animal models whose physiology, biology, and genetics more closely reflect specific human conditions. SAGE Labs is applying ZFN technology to achieve previously impossible genetic manipulations, such as tissue-specific gene deletion in rats."

Using the conditional knockout methodology, scientists at SAGE Labs have generated a pair of rat lines in which two important neuronal genes, Crhr1 and Grin1, were removed in specific neuronal populations. Crhr1 and Grin1 have been implicated as playing a role in depression and schizophrenia, respectively. The rat lines were developed through the SAGEspeed model creation process, which uses Sigma's CompoZr ZFN technology to create sophisticated genetic modifications in rats, mice, rabbits, and other organisms. CompoZr ZFN technology is the first to enable highly efficient, targeted editing of the genome of any species.

For more information and to request pricing, visit http://www.sageresearchmodels.com.

Cautionary Statement: The foregoing release contains forward-looking statements that can be identified by terminology such as "enable," "enabling," "leading to," "achieve," "predictive" or similar expressions, or by expressed or implied discussions regarding potential future revenues from products derived there from. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that iPS cells, iPS-cell derived primary cell lines, novel assays, or related custom services will assist the Company to achieve any particular levels of revenue in the future. In particular, management's expectations regarding products associated iPS cells, iPS-cell derived primary cell lines, novel assays, or related custom services could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; the Company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Company's assets and liabilities as recorded in its consolidated balance sheet, and other risks and factors referred to in Sigma-Aldrich's current Form 10-K on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Sigma-Aldrich is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sigma Life Science: Sigma Life Science is a Sigma-Aldrich business that represents the Company's leadership in innovative biological products and services for the global life science market and offers an array of biologically-rich products and reagents that researchers use in scientific investigation. Product areas include biomolecules, genomics and functional genomics, cells and cell-based assays, transgenics, protein assays, stem cell research, epigenetics and custom services/oligonucleotides. Sigma Life Science also provides an extensive range critical bioessentials like biochemicals, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, amino acids and their derivatives, and cell culture media.

About Sigma-Aldrich: Sigma-Aldrich is a leading Life Science and High Technology company whose biochemical, organic chemical products, kits and services are used in scientific research, including genomic and proteomic research, biotechnology, pharmaceutical development, the diagnosis of disease and as key components in pharmaceutical, diagnostics and high technology manufacturing. Sigma-Aldrich customers include more than 1.3 million scientists and technologists in life science companies, university and government institutions, hospitals and industry. The Company operates in 40 countries and has nearly 9,000 employees whose objective is to provide excellent service worldwide. Sigma-Aldrich is committed to accelerating customer success through innovation and leadership in Life Science and High Technology. For more information about Sigma-Aldrich, please visit its website at http://www.sigma-aldrich.com.

Sigma-Aldrich and Sigma are trademarks of Sigma-Aldrich Co, LLC registered in the US and other countries. SAGE and CompoZr are registered trademarks of Sigma-Aldrich Co. LLC. SAGEspeed is a trademark of Sigma-Aldrich Co. LLC.

SOURCE: Sigma-Aldrich Corporation

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SAGE® Labs Creates The First Tissue-Specific Gene Deletion In Rats

Public release date: 28-Mar-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY -- A novel method for printing human cells onto surfaces in defined patterns can help advance research on tissue engineering and regeneration, as described in an article in Tissue Engineering, Part C, Methods, a peer-reviewed journal from Mary Ann Liebert, Inc (http://www.liebertpub.com). The article is available free online at the Tissue Engineering website (http://www.liebertpub.com/ten).

"Cell printing is one of the breakthrough technologies that will make the application of stem cells for tissue engineering feasible," says John Jansen, DDS, PhD, Methods Co-Editor-in-Chief and Professor and Chairman, Department of Biomaterials, Radboud University Nijmegen Medical Center, The Netherlands.

Yu Fang and colleagues, University of Michigan, Ann Arbor, combined two microscale techniques to dispense and position cells in a variety of patterns. They then demonstrated the ability to use these 3-dimensional cell systems to monitor cell signaling events known to have a role in the growth, proliferation, and metastasis of cancer cells. The authors describe the use of sound waves to deliver microdroplets of cells and polymer-based phase separation to control cell placement in the article "Rapid Generation of Multiplexed Cell Co-Cultures Using Acoustic Droplet Ejection Followed by Aqueous Two-phase Exclusion Patterning." (http://online.liebertpub.com/doi/abs/10.1089/ten.TEC.2011.0709)

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About the Journal

Tissue Engineering (http://www.liebertpub.com/ten) is an authoritative peer-reviewed journal published monthly in print and online in three parts: Part A--the flagship journal; Part BReviews; and Part CMethods. Led by Co-Editors-In-Chief Antonios Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX, and Peter C. Johnson, MD, Vice President, Research and Development, Avery Dennison Medical Solutions of Chicago, IL and President and CEO, Scintellix, LLC, Raleigh, NC, the Journal brings together scientific and medical experts in the fields of biomedical engineering, material science, molecular and cellular biology, and genetic engineering. Tissue Engineering is the official journal of the Tissue Engineering & Regenerative Medicine International Society (TERMIS). Complete tables of content and a sample issue may be viewed online at the Tissue Engineering website (http://www.liebertpub.com/ten).

About the Company

Mary Ann Liebert, Inc.(http://www.liebertpub.com), is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Stem Cells and Development, Human Gene Therapy and HGT Methods, and Biopreservation and Biobanking. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available at Mary Ann Liebert Inc. (http://www.liebertpub.com).

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Innovative cell printing technologies hold promise for tissue engineering R&D

- Human genome and mouse studies identify new precise genetic links

Newswise Working with genetically engineered mice and the genomes of thousands of people with schizophrenia, researchers at Johns Hopkins say they now better understand how both nature and nurture can affect ones risks for schizophrenia and abnormal brain development in general.

The researchers reported in the March 2 issue of Cell that defects in a schizophrenia-risk genes and environmental stress right after birth together can lead to abnormal brain development and raise the likelihood of developing schizophrenia by nearly one and half times.

Our study suggests that if people have a single genetic risk factor alone or a traumatic environment in very early childhood alone, they may not develop mental disorders like schizophrenia, says Guo-li Ming, M.D., Ph.D., professor of neurology and member of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. But the findings also suggest that someone who carries the genetic risk factor and experiences certain kinds of stress early in life may be more likely to develop the disease.

Pinpointing the cause or causes of schizophrenia has been notoriously difficult, owing to the likely interplay of multiple genes and environmental triggers, Ming says. Searching for clues at the molecular level, the Johns Hopkins team focused on the interaction of two factors long implicated in the disease: Disrupted-in-Schizophrenia 1 (DISC1) protein, which is important for brain development, and GABA, a brain chemical needed for normal brain function.

To find how these factors impact brain development and disease susceptibility, the researchers first engineered mice to have reduced levels of DISC1 protein in one type of neuron in the hippocampus, a region of the brain involved in learning, memory and mood regulation. Through a microscope, they saw that newborn mouse brain cells with reduced levels of DISC1 protein had similar sized and shaped neurons as those from mice with normal levels of DISC1 protein. To change the function of the chemical messenger GABA, the researchers engineered the same neurons in mice to have more effective GABA. Those brain cells looked much different than normal neurons, with longer appendages or projections. Newborn mice engineered with both the more effective GABA and reduced levels of DISC1 showed the longest projections, suggesting, Ming said, that defects in both DISC1 and GABA together could change the physiology of developing neurons for the worse.

Meanwhile, other researchers at University of Calgary and at the National Institute of Physiological Sciences in Japan had shown in newborn mice that changes in environment and routine stress can impede GABA from working properly during development. In the next set of experiments, the investigators paired reducing DISC1 levels and stress in mice to see if it could also lead to developmental defects. To stress the mice, the team separated newborns from their mothers for three hours a day for ten days, then examined neurons from the stressed newborns and saw no differences in their size, shape and organization compared with unstressed mice. But when they similarly stressed newborn mice with reduced DISC1 levels, the neurons they saw were larger, more disorganized and had more projections than the unstressed mouse neurons. The projections, in fact, went to the wrong places in the brain.

Next, to see if their results in mice correlated to suspected human schizophrenia risk factors, the researchers compared the genetic sequences of 2,961 schizophrenia patients and healthy people from Scotland, Germany and the United States. Specifically, they determined if specific variations of DNA letters found in two genes, DISC1 and a gene for another protein, NKCC1, which controls the effect of GABA, were more likely to be found in schizophrenia patients than in healthy individuals. They paired 36 DNA letter changes in DISC1 and two DNA letter variations in NKCC1 one DNA letter change per gene in all possible combinations. Results showed that if a persons genome contained one specific combination of single DNA letter changes, then that person is 1.4 times more likely than people without these DNA changes to develop schizophrenia. Having these single DNA letter changes in either one of these genes alone did not increase risk.

Now that we have identified the precise genetic risks, we can rationally search for drugs that correct these defects, says Hongjun Song, Ph.D., co-author, professor of neurology and director of the Stem Cell Program at the Institute for Cell Engineering.

Other authors of the paper from Johns Hopkins are Ju Young Kim, Cindy Y. Liu, Fengyu Zhang, Xin Duan, Zhexing Wen, Juan Song, Kimberly Christian and Daniel R. Weinberger. Emer Feighery, Bai Lu and Joseph H. Callicott from the National Institute of Mental Health, Dan Rujescu of Ludwig-Maximilians-University, and David St Clair of the University of Aberdeen Royal Cornhill Hospital are additional authors.

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Genetic Risk and Stressful Early Infancy Join to Increase Risk for Schizophrenia

There is a tremendous opportunity in genetic medicine for innovation and for new players to make significant contributions, because it is still experimental, noted biologist and Nobel Laureate Dr David Baltimore said yesterday.
“Today, it is mainly the province of biotechnology companies and universities, not big pharmaceutical companies,” he observed in a keynote presentation at the Qatar International Conference on Stem Cell Science and Policy 2012.
There are new genetic tools available – though they are still experimental - to treat diseases which involve adding, subtracting or modifying genes in the cells of the body.
“However, they are powerful tools and I am confident they will be an important part of the medicine of the future,” he said.
Speaking on ‘The hematopoietic stem cell (HSC) as a target for therapy against cancer and Aids,’ Dr Baltimore explained that HSCs are one of the few cell types routinely used for bone marrow transplant.
The HSCs are easily accessible, retroviruses can be used to carry genes into these stem cells, the genes are then expressed in all of cells that derive from the HSC and can correct inherited defects and bring genes that perform therapy under a programme called engineering immunity.
“Though the human immune system is a wondrous creation of evolution yet it is not without certain limitations. One, in particular, is its poor ability to stop the growth of cancer cells– another is its hosting of HIV.
“In the case of cancer, the machinery of immunity can attack cancers but it rarely attacks with the necessary power. For HIV, the ability of the virus to use the CD4 and CCR5 proteins as receptors means that CD4 cells are the major cell type in which the virus grows.
“We have been trying to supply genes to the immune system by gene transfer methods that would improve its ability to block cancer and block infection of CD4 cells by HIV.
“For cancer, we have focused on T cell receptor genes. For HIV, we have used a small interfering ribonucleic acid (siRNA) targeted to CCR5. We have been quite successful in mice with both strategies and are now moving to humans.
“In both cases, our experiments with mice have focused on putting genes into HSCs as, once these cells are altered, they provide modified blood cells to the body for life.
“In our human cancer trials we first used peripheral T cells for modification with dramatic effect but it has been transient.
“We are now moving to stem cells. For the siRNA against CCR5, we plan to initiate trials within six months using autologous, gene-modified stem cells,” he added.
The ensuing panel discussion on ‘Opportunities and challenges for stem cell research,’ saw Prof Irving Weissman (Stanford Institute for Stem Cell Biology and Regenerative Medicine) cautioning against ‘phoney organisations engaged in stem cell therapy.’
Prof Juan Carlos Izpisua Belmonte (Salk Institute for Biological Studies, US) stated that stem cells derived from umbilical cord blood should be considered as one of the key cells for use in regenerative medicine.
The session also featured Dr Alan Trounson (California Institute of Regenerative Medicine), Prof Roger Pedersen (The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge), Dr Lawrence Corey (University of Washington) and with Dr Richard Klausner (managing partner of biotechnology venture capital firm The Column Group) as moderator.
Earlier, Ambassador Edward P Djerejian (founding director, James A Baker III Institute for Public Policy, Rice University, Houston, Texas, US) spoke about the collaboration with Qatar Foundation on stem cell research.

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‘Scope for innovation in genetic medicine’

Public release date: 15-Feb-2012
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Contact: Cathia Falvey
cfalvey@liebertpub.com
914-740-2100
Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, February 15, 2012?Therapeutic cancer vaccines, which stimulate the body's immune system to target and destroy cancer cells, are being used in combination with conventional chemotherapy with growing success, as described in several illuminating articles in Cancer Biotherapy and Radiopharmaceuticals, a peer-reviewed journal from Mary Ann Liebert, Inc. (http://www.liebertpub.com). These articles are available free online at http://www.liebertpub.com/cbr

The U.S. FDA recently approved the first cancer therapeutic vaccine for treatment of metastatic prostate cancer. At least 14 other cancer vaccine strategies are in Phase II or III clinical trials for metastatic melanoma, lung cancer, and lymphoma, for example.

A critical perspective, "Recent Advances in Therapeutic Cancer Vaccines," (http://online.liebertpub.com/doi/full/10.1089/cbr.2012.1200) published in the Journal by Jeffrey Schlom, PhD, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD explains that a key advantage of cancer vaccines used in combination with chemotherapy is the extremely low level of toxicity. "The next frontier for vaccine therapy will be the use of vaccines in combination with certain chemotherapeutic agents, radiation, hormone therapy, and certain small molecule targeted therapies," according to Dr. Schlom.

These emerging areas of cancer vaccine therapy are explored in detail in two accompanying research reports by Dr. Schlom's colleagues at NCI/NIH. James Hodge, Hadley Sharp, and Sofia Gameiro describe how a tumor-targeted vaccine can enhance the effectiveness of radiation therapy on cancer growth and spread beyond the primary tumor in the article "Abscopal Regression of Antigen Disparate Tumors by Antigen Cascade After Systemic Tumor Vaccination in Combination with Local Tumor Radiation." (http://online.liebertpub.com/doi/abs/10.1089/cbr.2012.1202) Drs. Hodge and Gameiro and coauthor Jorge Caballero present the molecular signatures of lung tumor cells that can be made more susceptible to immunotherapy when first exposed to chemotherapeutic agents in the article "Defining the Molecular Signature of Chemotherapy-Mediated Lung Tumor Phenotype Modulation and Increased Susceptibility to T-cell Killing." (http://online.liebertpub.com/doi/abs/10.1089/cbr.2012.1203)

"This perspective and promising research reports are from one of the leading vaccine research laboratories in the world," says Co-Editor-in-Chief Donald J. Buchsbaum, PhD, Division of Radiation Biology, Department of Radiation Oncology, University of Alabama at Birmingham. "The ultimate use of cancer vaccines in combination with other immunotherapies, chemotherapy, or radiation therapy will be based on preclinical investigations and hopefully will produce clinical survival benefit for a range of cancers."

###

Cancer Biotherapy and Radiopharmaceuticals, published 10 times a year in print and online, is under the editorial leadership of Editors Donald J. Buchsbaum, PhD and Robert K. Oldham, MD, Lower Keys Cancer Center, Key West, FL. Cancer Biotherapy and Radiopharmaceuticals is the only journal with a specific focus on cancer biotherapy, including monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapy. The Journal includes extensive reporting on advancements in radioimmunotherapy and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments. Topics include antibody drug conjugates, fusion toxins and immunotoxins, nanoparticle therapy, vascular therapy, and inhibitors of proliferation signaling pathways. Complete tables of content and a sample issue may be viewed online at http://www.liebertpub.com/cbr

Mary Ann Liebert, Inc. is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Journal of Interferon & Cytokine Research; Human Gene Therapy and Human Gene Therapy Methods; and Stem Cells and Development. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available at http://www.liebertpub.com

Mary Ann Liebert, Inc.
140 Huguenot St., New Rochelle, NY 10801-5215
http://www.liebertpub.com
Phone: 914-740-2100
800M-LIEBERT
Fax: 914-740-2101

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Promising early results with therapeutic cancer vaccines

Your life depends on purposeful, targeted changes to cellular DNA. Although conventional thinking says directed DNA changes are impossible, the truth is that you could not survive without them. Your immune system needs to engineer certain DNA sequences in just the right way to function properly.

Today's blog is a tale of how cells engineer their DNA molecules for a specific purpose. It also illustrates how an evolutionary process works within the human body.

Your immune system has to anticipate and inactivate unknown invaders. Living organisms deal with unpredictable events by evolving. They change to adapt to new circumstances. Variation comes from their capacity for self-modification. Cells have many molecular mechanisms that read, write, and reorganize the information in their genomes, the DNA molecules used for data storage.

The adaptive immune system executes basic evolutionary principles in real time. It has to recognize and combat unknown (and utterly unpredictable) invaders. Immune system cells have to produce antibody molecules that can bind to any possible molecular structure.

How do cells with finite DNA, and finite coding capacity, produce a virtually infinite variety of antibodies? The answer is that certain immune cells (B cells) become rapid evolution factories. They generate antibodies with effectively limitless diversity while preserving molecular structures needed to interact with other parts of the immune system.

Immune cells achieve both diversity and regularity in antibody structures. They accomplish this by a targeted yet flexible process of natural genetic engineering: they cut and splice DNA.

Diversity is strictly limited to a special part of the antibody molecules: a "variable" region encoded by engineered DNA. DNA encoding the "constant" region does not change in the same way. The diversity-generating process is called "VDJ recombination" because it involves cutting and splicing together different "variable" (V), "diversity" (D) and "joining" (J) coding segments. Immune cells do this by cutting DNA at defined "recombination signal sequences." There are hundreds of V segments, about a few dozen D segments, and ten J segments. The various combinations of different spliced segments makes for a tremendous amount of diversity.

Antibodies contain two paired protein chains: a longer heavy chain and a shorter light chain. The heavy chain variable coding region forms by splicing V, D, and J segments together. The light chain variable coding region forms by joining V and J segments together. There are at least 10,000 VDJ combinations and 1,000 VJ combinations. Altogether, over 10,000,000 different heavy + light chain antibodies are possible through "combinatorial diversity."

Not bad... but not good enough.

VDJ recombination generates additional diversity. Although cutting the V, D, and J segments is precise, immune cells join each pair of cleaved DNA segments at about a dozen different positions. Connection between the same two segments can have about 30 to 35 possible different sequence outcomes. This "junctional diversity" adds over 1,000 possible antibody combinations.

In addition, heavy chain D segment joining has another virtually unlimited source of variability. Immune cells have an enzyme that attaches unique new DNA sequences to either end of the D segment. These are not encoded anywhere in the genome. Such so-called "N region" sequences can add over 1,000 new variations to each existing VDJ combination.

So the total possible genetically engineered antibody diversity is something above 10,000,000 X 1,000 X 1,000 = 10,000,000,000,000 combinations. This extraordinary number appears to be large enough to generate antibodies that can protect you from virtually any invader, whatever its molecular structure may be.

The immune system is itself a rapid evolutionary process, replacing one set of immune specificities with another. The right antibody-producing cells multiply when an invader enters the body. Antibodies sit on the surface of cells that made them. When a particular variable region binds an invader, that event sends a signal inside the cell to begin dividing.

Dividing immune cells are called "activated B cells," which proliferate into distinct populations. Because the descendants of a single activated B cell share the same engineered variable region coding sequences, they produce even more invader-recognizing antibodies. By binding, these antibodies signal the rest of the immune system to begin eliminating the invaders. This is the front-line "primary" adaptive immune response.

In a future blog, I'll explain ongoing natural genetic engineering as activated immune cells mature in the "secondary" response. It is no less amazing. For now, let's draw three conclusions from the initial rapid evolution system. We see that:

Evolution has produced a system that engineers DNA with a specific purpose: encoding proteins that bind to unpredictable invaders and signal the immune system to make more antibodies and eliminate the invaders. Precise targeting of DNA cutting to variable region-coding segments allows the basic antibody structure to stay the same. At the same time, its recognition/binding capacity changes. Your B cells are able to combine several different kinds of DNA biochemistry into a functional engineering process: 1) cutting the V, D and J segments; 2) joining the cleaved segments; and 3) synthesizing and inserting the N region sequences.

In the immune system, "purposeful" and "having a predestined outcome" are far from the same thing. Your immune system follows a regular process, but the end result is not fixed in advance. This is an important lesson to keep in mind as we witness ongoing public debates over evolutionary DNA change.

In biology, the alternative to randomness is not necessarily strict determinism. If the cells of the immune system can use well-defined natural genetic engineering processes to make change when change is needed, there is a scientific basis for saying that germ-line cells might do the same in the course of evolution.

Read more here:
James A. Shapiro: Purposeful, Targeted Genetic Engineering in Immune System Evolution

(06-18) 13:42 PDT SAN FRANCISCO -- Dr. Shinya Yamanaka, a stem cell researcher at UCSF's Gladstone Institutes who discovered a technique for transforming adult skin cells into "pluripotent" stem cells without resorting to human embryos, has won Japan's $550,000 Kyoto Prize, an international award that honors scientific, cultural and spiritual contributions to human knowledge.

His discovery resulted in a class of much-sought stem cells that scientists can induce to become virtually any other type of functioning human cell that one day might be used to treat varied diseases or injuries.

During their research, Yamanaka and his colleagues altered the genetics of adult skin cells by inserting four specific viral genes that produce proteins known as transcription factors into the cells. Those proteins in turn yielded other genes that reprogrammed the skin cells so they acquired all the characteristics that made them what are now known as induced pluripotent cells.

Before his discovery, those pluripotent human stem cells could only be harvested from human embryos, a source posing such powerful ethical issues that former President George W. Bush banned virtually all embryonic stem cell research eight years ago. The ban remained in force until President Obama reversed it last year.

Yamanaka, 47, who is attending the annual meeting of the International Society of Stem Cell Research in San Francisco this week, was not told of his award until just before midnight Pacific time on Thursday.

The Kyoto Prize is awarded annually by Japan's Inamori Foundation for major discoveries in many fields of advanced technology, and four other Bay Area scientists have won it in recent years.

They are Leonard Herzenberg, a Stanford geneticist and immunologist who developed a revolutionary cell-sorting machine now crucial to advanced biomedical research; Alan Kay, a Silicon Valley pioneer at Hewlett-Packard who led advanced computing technology for 40 years; Donald E. Knuth, a Stanford information technology expert and specialist in computer programming, language analysis and computerized printing and Richard Karp, a UC Berkeley computer scientist and pioneer in computational biology.

In addition to heading his laboratory at the Gladstone Institute for Cardiovascular Research on the Mission Bay campus of UCSF, Yamanaka is also a professor at Kyoto University, where he began his efforts seeking a way of transforming adult cells.

Besides resolving ethical issues by his achievement, Yamanaka's success also means that the pluripotent stem cells needed to treat a patient's disease can be obtained from the ordinary skin cells of a patient's own body - thus making stem cell therapy possible without the hazards involved in immunologic rejection of cells from other people.

Robert Lanza, chief scientific officer of Advanced Cell Technology and an adjunct professor at Wake Forest University's stem cell research center, said recently that Yamanaka's work "is likely to be the most important stem cell breakthrough of all time."

"The ability to generate an unlimited supply of patient-specific stem cells will revolutionize the future of medicine," Lanza said.

Read more: http://www.sfgate.com