Referenced Stocks: ILMN, LIFE, TMO

Given the recent flurry of activities, it seems that Life Technologies Corporation ( LIFE ) is focused on strengthening its foothold in the field of stem cell research. The company recently signed a non-exclusive agreement with iPS Academia of Japan for its induced pluripotent stem (iPS) cell patent portfolio. Based on this agreement, the company will be able to expand its portfolio for the iPS cell research community.

Besides, it is well placed to create iPS cells and differentiate them into various cell types to be used in drug discovery and pre-clinical research. The license also enables Life Technologies to provide creation, differentiation and screening services of iPS cell to scientists globally. We consider the agreement to be a significant achievement for the company in the field of stem cell research as iPS cells are gaining attention for use in the areas of drug discovery, disease research and other areas of biotechnology.

The agreement with iPS Academia of Japan comes on the heels of the partnership with Cellular Dynamics International, the world's largest producer of human cells derived from iPS cells. The partnership will aim at commercializing a set of three new products optimized to consistently develop and grow human iPS cells for both research and bioproduction.

These initiatives undertaken by Life Technologies should strengthen its Research Consumables segment. This segment includes molecular and cell biology reagents, endpoint PCR and other benchtop instruments and consumables. These products include RNAi, DNA synthesis, sample prep, transfection, cloning and protein expression profiling and protein analysis, cell culture media used in research, stem cells and related tools, cellular imaging products, antibodies and cell therapy related products. In the most recent quarter, this division recorded a 4% year-over-year increase in revenues to $420 million on the back of growth in cell culture workflow products, endpoint PCR products and molecular and cell biology consumables.

Life Technologies enjoys a strong position in the life sciences market, though management prefers to maintain a cautious but optimistic outlook for the remainder of the year. We are encouraged by the improvement in margins amidst the tight competitive scenario with the presence of players such as Thermo Fisher Scientific ( TMO ), Illumina ( ILMN ), among others.

We have a Neutral recommendation on Life Technologies. The stock retains a Zacks #3 Rank (hold) in the short term.

The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of The NASDAQ OMX Group, Inc.

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LIFE Focuses on Stem Cell Research - Analyst Blog

CARLSBAD, Calif., June 12, 2012 /PRNewswire/ -- Life Technologies Corporation (LIFE) today announced a partnership with Cellular Dynamics International (CDI), the world's largest producer of human cells derived from induced pluripotent stem (iPS) cells, to commercialize a set of three new products optimized to consistently develop and grow human iPS cells for both research and bioproduction.

The partnership marries CDI's leadership in human iPS cell development with Life Technologies' expertise in stem cell research tool manufacturing and global distribution network to make these novel technologies accessible to researchers around the world. Life Technologies' commercialization of Essential 8 Medium, Vitronectin (VTN-N), and Episomal iPSC Reprogramming Vectors addresses several challenges associated with developing relevant cells for use in a wide range of studies, from basic and translational research to drug discovery efforts. The effectiveness of these products is the focus of recent validation studies published in the journals Nature Methods and PLoS One.

"The launch of these new stem cell culture products 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," noted Bob Palay, CDI Chief Executive Officer.

To eliminate the variability introduced by a mouse cell feeder layer previously used during the culture of human iPS cells, researchers have adopted "feeder-free" media. However, existing feeder-free culture media contain more than 20 interactive ingredients, many of which, such as bovine serum albumin (BSA) and lipids, are highly uncharacterized and vary significantly from lot-to-lot.This leads to variability in iPS cell growth and differentiation and impedes the progress of disease studies and potential clinical applications.

Essential 8 Medium, manufactured in a Life Technologies current Good Manufacturing Practices (cGMP) facility, overcomes this barrier. In addition, BSA and other undesirable components have been removed from the media, thus reducing the number of ingredients to just eight well-characterized elements required to support efficient growth, eliminate variability, and enable large-scale production of human iPS cells.

"Essential 8 has far fewer variables, it's more straight-forward and a lot more reproducible," said Emile Nuwaysir, Ph.D., Chief Operating Officer and Vice President of Cellular Dynamics International. "If the goal is to make a billion cardiomyocytes a day, every day, you want to make sure they're all the same. That's virtually impossible using mouse embryonic fibroblasts and it's very difficult using the more complex, feeder-free media that were available before Essential 8."

Optimized for use with Essential 8 Medium, Vitronectin (VTN-N) is a defined, human protein-based substrate that further eliminates variability during iPS cell culture unlike most existing feeder-free media that requires the use of an undefined matrix derived from mouse tumor cells for cell attachment and growth. The combination of Essential 8 Medium and Vitronectin (VTN-N) provides a defined, culture system free of non-human components for robust, cost-effective and scalable iPS cell culture.

Life Technologies is also introducing the Episomal iPSC Reprogramming Vectors, which leverages non-viral, non-integrating technology to deliver six genes to initiate the reprogramming of human somatic cells, such as blood and skin cells, to iPS cells. A non-viral approach offers a key advantage: human-derived iPS cells have more relevance for patient-specific, disease research. Traditional viral-based methods, such as lentivirus or retrovirus, require integration into the host genome for replication and can disrupt the genome of the reprogrammed cells.

"The ability to reproducibly establish andculture iPS cells using defined reagent systems is key for the advancement of stem cell research, disease modeling and drug discovery," said Chris Armstrong Ph.D, General Manager and Vice President of Primary and Stem Cell Systems at Life Technologies. "The commercialization of these exciting new products serves that purpose and underscores our commitment to provide the most innovative and relevant workflow tools to our customers."

All three products were developed at the University of Wisconsin by Dr. James Thomson, whose lab pioneered embryonic stem cell research and much of the technology surrounding stem cell culturing conditions, in vitro differentiation and iPS cell generation.

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Life Technologies and Cellular Dynamics International Partner for Global Commercialization of Novel Stem Cell ...

SAN DIEGO , June 11, 2012 /CNW/ - Fate Therapeutics, Inc. in collaboration with BD Biosciences, a segment of BD (Becton, Dickinson and Company), today announced the introduction of the first induced pluripotent stem cell (iPSC)-related product resulting from the collaboration between the two companies. BD SMC4 is a patent protected, pre-formulated cocktail of small molecules for improving cellular reprogramming efficiencies and for enabling single-cell passaging and flow cytometry sorting of iPSCs in feeder cell-free and other pluripotent cell culture systems.

"iPSCs have the potential to redefine the way medical research is conducted," said Dr. Charles Crespi , Vice President at BD Biosciences. "However, most current reprogramming technologies are inefficient, which slows research efforts. BD SMC4 is an exciting complement to the BD portfolio of stem cell technologies that can accelerate the pace of research, and, ultimately, drug development."

The collaboration between BD Biosciences and Fate Therapeutics seeks to provide life science researchers and the pharmaceutical community reliable access to advanced iPSC tools and technologies. These technologies are for use in human disease research, drug discovery and the manufacture of cell-based therapies. The identification of the small molecule additives, and their use in an industrial platform for iPSC generation and characterization was recently published in the journal, Scientific Reports (Valamehr et al Scientific Reports 2, Article number: 213, 2012).

"Our research focus has uncovered novel technologies to enable the commercial and industrial application of iPS cells," said Dr. Peter Flynn , Vice President of Biologic Therapeutics at Fate Therapeutics. "The BD SMC4 media additive was developed at Fate to enable our scientists to internally perform high-throughput generation, clonal selection, characterization and expansion of pluripotent cells, and we are excited to empower the stem cell research community with these important iPSC technologies through our collaboration with BD."

iPSC technology holds great promise for disease modeling, drug screening and toxicology testing as well as for autologous and allogeneic cell therapy. Building on the foundational work of its scientific founders, Drs. Rudolf Jaenisch and Sheng Ding, Fate Therapeutics is developing a suite of proprietary products and technologies to overcome the remaining technical hurdles for iPS cell integration into the therapeutic development process. Under the three-year collaboration, Fate and BD will co-develop certain stem cell products using Fate's award-winning iPSC technology platform, and BD will commercialize these stem cell products on a worldwide basis. The iPSC product platform of Fate Therapeutics is supported by foundational intellectual property including U.S. Patent No. 8,071,369, entitled "Compositions for Reprogramming Somatic Cells," which claims a composition comprising a somatic cell having an exogenous nucleic acid that encodes an Oct4 protein introduced into the cell.

About Fate Therapeutics, Inc. Fate Therapeutics is an innovative biotechnology company developing novel stem cell modulators (SCMs), biologic or small molecule compounds that guide cell fate, to treat patients with very few therapeutic options. Fate Therapeutics' lead clinical program, ProHema, consists of pharmacologically-enhanced hematopoietic stem cells (HSCs), designed to improve HSC support during the normal course of a stem cell transplant for the treatment of patients with hematologic malignancies. The Company is also advancing a robust pipeline of human recombinant proteins, each with novel mechanisms of action, for skeletal muscle, beta-islet cell, and post-ischemic tissue regeneration. Fate Therapeutics also applies its award-winning, proprietary induced pluripotent stem cell (iPSC) technology to offer a highly efficient platform to recapitulate human physiology for commercial scale drug discovery and therapeutic use. Fate Therapeutics is headquartered in San Diego , CA, with a subsidiary in Ottawa , Canada . For more information, please visit http://www.fatetherapeutics.com.

About BDBD is a leading global medical technology company that develops, manufactures and sells medical devices, instrument systems and reagents. The Company is dedicated to improving people's health throughout the world. BD is focused on improving drug delivery, enhancing the quality and speed of diagnosing infectious diseases and cancers, and advancing research, discovery and production of new drugs and vaccines. BD's capabilities are instrumental in combating many of the world's most pressing diseases. Founded in 1897 and headquartered in Franklin Lakes , New Jersey, BD employs approximately 29,000 associates in more than 50 countries throughout the world. The Company serves healthcare institutions, life science researchers, clinical laboratories, the pharmaceutical industry and the general public. For more information, please visit http://www.bd.com.

SOURCE Fate Therapeutics, Inc.

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Fate Therapeutics And BD Biosciences Launch BD™ SMC4 To Improve Cellular Reprogramming And IPS Cell Culture Applications

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: 29-May-2012 [ | E-mail | Share ]

Contact: Tim Hawkins Tim.Hawkins@vai.org 616-234-5519 Van Andel Research Institute

Grand Rapids, Mich. (May 29, 2012) Researchers from South Korea, Sweden, and the United States have collaborated on a project to restore neuron function to parts of the brain damaged by Huntington's disease (HD) by successfully transplanting HD-induced pluripotent stem cells into animal models.

Induced pluripotent stem cells (iPSCs) can be genetically engineered from human somatic cells such as skin, and can be used to model numerous human diseases. They may also serve as sources of transplantable cells that can be used in novel cell therapies. In the latter case, the patient provides a sample of his or her own skin to the laboratory.

In the current study, experimental animals with damage to a deep brain structure called the striatum (an experimental model of HD) exhibited significant behavioral recovery after receiving transplanted iPS cells. The researchers hope that this approach eventually could be tested in patients for the treatment of HD.

"The unique features of the iPSC approach means that the transplanted cells will be genetically identical to the patient and therefore no medications that dampen the immune system to prevent graft rejection will be needed," said Jihwan Song, D.Phil. Associate Professor and Director of Laboratory of Developmental & Stem Cell Biology at CHA Stem Cell Institute, CHA University, Seoul, South Korea and co-author of the study.

The study, published online this week in Stem Cells, found that transplanted iPSCs initially formed neurons producing GABA, the chief inhibitory neurotransmitter in the mammalian central nervous system, which plays a critical role in regulating neuronal excitability and acts at inhibitory synapses in the brain. GABAergic neurons, located in the striatum, are the cell type most susceptible to degeneration in HD.

Another key point in the study involves the new disease models for HD presented by this method, allowing researchers to study the underlying disease process in detail. Being able to control disease development from such an early stage, using iPS cells, may provide important clues about the very start of disease development in HD. An animal model that closely imitates the real conditions of HD also opens up new and improved opportunities for drug screening.

"Having created a model that mimics HD progression from the initial stages of the disease provides us with a unique experimental platform to study Huntington's disease pathology" said Patrik Brundin, M.D., Ph.D., Director of the Center for Neurodegenerative Science at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University, Sweden, and co-author of the study.

Huntington's disease (HD) is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems. It typically becomes noticeable in mid-adult life, with symptoms beginning between 35 and 44 years of age. Life expectancy following onset of visual symptoms is about 20 years. The worldwide prevalence of HD is 5-10 cases per 100,000 persons. Key to the disease process is the formation of specific protein aggregates (essentially abnormal clumps) inside some neurons.

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Researchers restore neuron function to brains damaged by Huntington's disease

Public release date: 30-Apr-2012 [ | E-mail | Share ]

Contact: Vanessa McMains vmcmain1@jhmi.edu 410-502-9410 Johns Hopkins Medical Institutions

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 don't 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, Cheng's 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 body's 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.

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Improved adult-derived human stem cells have fewer genetic changes than expected

SOUTH SAN FRANCISCO, CA--(Marketwire -04/25/12)- VistaGen Therapeutics, Inc. (VSTA.OB - News) (VSTA.OB - News), a biotechnology company applying stem cell technology for drug rescue, has secured a new United States patent covering the company's proprietary methods used to measure and type the toxic effects produced by drug compounds in liver stem cells.

Test methods included in this new patent, (U.S. Patent 11/445,733), titled "Toxicity Typing Using Liver Stem Cells," cover all mammalian liver stem cells -- rat and mouse cells, for example, in addition to human cells. Liver stem cells used in drug testing can be derived from in vivo tissue or produced from embryonic stem cells (ES) or induced pluripotent stem cells (iPS).

H. Ralph Snodgrass, Ph.D., VistaGen's President and Chief Scientific Officer, said, "This patent covers the monitoring of changes in gene expression as an assay for predicting drug toxicities. It is well known that drugs activate and suppress specific genes, and that the changes in gene expression reflect the mechanism of drug toxicities. The specific sets of genes that are affected become a profile of that drug."

VistaGen's new patent also covers techniques used to develop a database of gene expression profiles of drugs that have the same type of liver toxicity. Using sophisticated "pattern matching" database tools, drug developers can analyze these related profiles to determine "gene expression signatures" that are common and predictive of drugs that produce specific types of toxicity.

"Without this database capability, a drug's single gene expression profile could not be interpreted," Dr. Snodgrass added. "The ability to use liver stem cells to differentiate drug-dependent gene expression profiles, and to compare those profiles of drugs known to induce toxic liver effects, provides a powerful tool for predicting liver toxicity of new drug candidates, including drug rescue variants."

Shawn K. Singh, VistaGen's Chief Executive Officer, stated, "Strong and enforceable intellectual property rights are critical components of our plan to optimize the commercial potential of our Human Clinical Trials in a Test Tube platform. This new liver toxicity typing patent further solidifies our growing IP portfolio, and supports the continuing development of LiverSafe 3D, our human liver cell-based bioassay system, which complements our CardioSafe 3D human heart cell-based bioassay system for heart toxicity."

About VistaGen Therapeutics

VistaGen is a biotechnology company applying human pluripotent stem cell technology for drug rescue and cell therapy. VistaGen's drug rescue activities combine its human pluripotent stem cell technology platform, Human Clinical Trials in a Test Tube, with modern medicinal chemistry to generate new chemical variants (Drug Rescue Variants) of once-promising small-molecule drug candidates. These are drug candidates discontinued due to heart toxicity after substantial development by pharmaceutical companies, the U.S. National Institutes of Health (NIH) or university laboratories. VistaGen uses its pluripotent stem cell technology to generate early indications, or predictions, of how humans will ultimately respond to new drug candidates before they are ever tested in humans, bringing human biology to the front end of the drug development process.

Additionally, VistaGen's small molecule drug candidate, AV-101, is in Phase 1b development for treatment of neuropathic pain. Neuropathic pain, a serious and chronic condition causing pain after an injury or disease of the peripheral or central nervous system, affects approximately 1.8 million people in the U.S. alone. VistaGen is also exploring opportunities to leverage its current Phase 1 clinical program to enable additional Phase 2 clinical studies of AV-101 for epilepsy, Parkinson's disease and depression. To date, VistaGen has been awarded over $8.5 million from the NIH for development of AV-101.

Visit VistaGen at http://www.VistaGen.com, follow VistaGen at http://www.twitter.com/VistaGen or view VistaGen's Facebook page at http://www.facebook.com/VistaGen

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VistaGen Secures Key U.S. Patent Covering Stem Cell Technology Methods Used to Test Drug Candidates for Liver Toxicity

April 20, 2012 18:19 PM

IBN Discovers Human Neural Stem Cells, Promising Discovery For Breast Cancer Therapy

By Tengku Noor Shamsiah Tengku Abdullah

SINGAPORE, April 20 (Bernama) -- Could engineered human stem cells hold the key to cancer survival?

Scientists at the Institute of Bioengineering and Nanotechnology (IBN), the world's first bioengineering and nanotechnology research institute, have discovered that neural stem cells possess the innate ability to target tumor cells outside the central nervous system.

This finding, which was demonstrated successfully on breast cancer cells, was recently published in leading peer reviewed journal, Stem Cells.

Despite decades of cancer research, cancer remains a leading cause of death worldwide, accounting for 7.6 million deaths in 2008, and breast cancer is one of the most common causes of cancer deaths each year.

In Singapore, more than 1,400 women are diagnosed with breast cancer and more than 300 die as a result of breast cancer annually.

A team of researchers led by IBN group leader Dr Shu Wang, has made a landmark discovery that neural stem cells (NSCs) derived from human induced pluripotent stem (iPS) cells could be used to treat breast cancer.

The effectiveness of using NSCs, which originate from the central nervous system, to treat brain tumors has been investigated in previous studies.

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IBN Discovers Human Neural Stem Cells, Promising Discovery For Breast Cancer Therapy

Despite decades of cancer research, cancer remains a leading cause of death worldwide, accounting for 7.6 million deaths in 2008, and breast cancer is one of the most common causes of cancer deaths each year . In Singapore, more than 1,400 women are diagnosed with breast cancer and more than 300 die as a result of breast cancer each year . The high fatality rate of cancer is partially attributed to the invasive ability of malignant tumors to spread throughout the human body, and the ineffectiveness of conventional therapies to eradicate the cancer cells.

A team of researchers led by IBN Group Leader, Dr Shu Wang, has made a landmark discovery that neural stem cells (NSCs) derived from human induced pluripotent stem (iPS) cells could be used to treat breast cancer. The effectiveness of using NSCs, which originate from the central nervous system, to treat brain tumors has been investigated in previous studies. This is the first study that demonstrates that iPS cell-derived NSCs could also target tumors outside the central nervous system, to treat both primary and secondary tumors.

To test the efficiency of NSCs in targeting and treating breast cancer, the researchers injected NSCs loaded with a suicide gene (herpes simplex virus thymidine) into mice bearing breast tumors. They did this using baculoviral vectors or gene carriers engineered from an insect virus (baculovirus), which does not replicate in human cells, making the carriers less harmful for clinical use. A prodrug (ganciclovir), which would activate the suicide gene to kill the cancerous cells upon contact, was subsequently injected into the mice. A dual-colored whole body imaging technology was then used to track the distribution and migration of the iPS-NSCs.

The imaging results revealed that the iPS-NSCs homed in on the breast tumors in the mice, and also accumulated in various organs infiltrated by the cancer cells such as the lung, stomach and bone. The survival of the tumor-bearing mice was prolonged from 34 days to 39 days. This data supports and explains how engineered iPS-NSCs are able to effectively seek out and inhibit tumor growth and proliferation.

Dr Shu Wang shared, "We have demonstrated that tumor-targeting neural stem cells may be derived from human iPS cells, and that these cells may be used in combination with a therapeutic gene to cripple tumor growth. This is a significant finding for stem cell-based cancer therapy, and we will continue to improve and optimize our neural stem cell system by preventing any unwanted activation of the therapeutic gene in non-tumor regions and minimizing possible side effects."

"IBN's expertise in generating human stem cells from iPS cells and our novel use of insect virus carriers for gene delivery have paved the way for the development of innovative stem cell-based therapies. With their two-pronged attack on tumors using genetically engineered neural stem cells, our researchers have discovered a promising alternative to conventional cancer treatment," added Professor Jackie. Y. Ying, IBN Executive Director.

Compared to collecting and expanding primary cells from individual patients, IBN's approach of using iPS cells to derive NSCs is less laborious and suitable for large-scale manufacture of uniform batches of cellular products for repeated patient treatments. Importantly, this approach will help eliminate variability in the quality of the cellular products, thus facilitating reliable comparative analysis of clinical outcomes.

Additionally, these iPS cell-derived NSCs are derived from adult cells, which bypass the sensitive ethical issue surrounding the use of human embryos, and since iPS cells are developed from a patient's own cells, the likelihood of immune rejection would be reduced.

References: 1. J. Yang, D. H. Lam, S. S. Goh, E. X. L. Lee, Y. Zhao, F. Chang Tay, C. Chen, S. Du, G. Balasundaram, M. Shahbazi, C. K. Tham, W. H. Ng, H. C. Toh and S. Wang, "Tumor Tropism of Intravenously Injected Human Induced Pluripotent Stem Cell-derived Neural Stem Cells and their Gene Therapy Application in a Metastatic Breast Cancer Model," Stem Cells, (2012) DOI: 10.1002/stem.1051.

2. E. X. Lee, D. H. Lam, C. Wu, J. Yang, C. K. Tham and S. Wang, "Glioma Gene Therapy Using Induced Pluripotent Stem Cell-Derived Neural Stem Cells," Molecular Pharmaceutics, 8 (2011) 1515-1524.

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IBN Discovers Human Neural Stem Cells with Tumor Targeting Ability - A Promising Discovery for Breast Cancer Therapy

ScienceDaily (Apr. 20, 2012) Could engineered human stem cells hold the key to cancer survival? Scientists at the Institute of Bioengineering and Nanotechnology (IBN), the world's first bioengineering and nanotechnology research institute, have discovered that neural stem cells possess the innate ability to target tumor cells outside the central nervous system.

This finding, which was demonstrated successfully on breast cancer cells, was recently published in peer reviewed journal, Stem Cells.

Despite decades of cancer research, cancer remains a leading cause of death worldwide, accounting for 7.6 million deaths in 2008, and breast cancer is one of the most common causes of cancer deaths each year[1]. In Singapore, more than 1,400 women are diagnosed with breast cancer and more than 300 die as a result of breast cancer each year[2]. The high fatality rate of cancer is partially attributed to the invasive ability of malignant tumors to spread throughout the human body, and the ineffectiveness of conventional therapies to eradicate the cancer cells.

A team of researchers led by IBN Group Leader, Dr Shu Wang, has made a landmark discovery that neural stem cells (NSCs) derived from human induced pluripotent stem (iPS) cells could be used to treat breast cancer. The effectiveness of using NSCs, which originate from the central nervous system, to treat brain tumors has been investigated in previous studies. This is the first study that demonstrates that iPS cell-derived NSCs could also target tumors outside the central nervous system, to treat both primary and secondary tumors.

To test the efficiency of NSCs in targeting and treating breast cancer, the researchers injected NSCs loaded with a suicide gene (herpes simplex virus thymidine) into mice bearing breast tumors. They did this using baculoviral vectors or gene carriers engineered from an insect virus (baculovirus), which does not replicate in human cells, making the carriers less harmful for clinical use. A prodrug (ganciclovir), which would activate the suicide gene to kill the cancerous cells upon contact, was subsequently injected into the mice. A dual-colored whole body imaging technology was then used to track the distribution and migration of the iPS-NSCs.

The imaging results revealed that the iPS-NSCs homed in on the breast tumors in the mice, and also accumulated in various organs infiltrated by the cancer cells such as the lung, stomach and bone. The survival of the tumor-bearing mice was prolonged from 34 days to 39 days. This data supports and explains how engineered iPS-NSCs are able to effectively seek out and inhibit tumor growth and proliferation.

Dr Shu Wang shared, "We have demonstrated that tumor-targeting neural stem cells may be derived from human iPS cells, and that these cells may be used in combination with a therapeutic gene to cripple tumor growth. This is a significant finding for stem cell-based cancer therapy, and we will continue to improve and optimize our neural stem cell system by preventing any unwanted activation of the therapeutic gene in non-tumor regions and minimizing possible side effects."

"IBN's expertise in generating human stem cells from iPS cells and our novel use of insect virus carriers for gene delivery have paved the way for the development of innovative stem cell-based therapies. With their two-pronged attack on tumors using genetically engineered neural stem cells, our researchers have discovered a promising alternative to conventional cancer treatment," added Professor Jackie. Y. Ying, IBN Executive Director.

Compared to collecting and expanding primary cells from individual patients, IBN's approach of using iPS cells to derive NSCs is less laborious and suitable for large-scale manufacture of uniform batches of cellular products for repeated patient treatments. Importantly, this approach will help eliminate variability in the quality of the cellular products, thus facilitating reliable comparative analysis of clinical outcomes.

Additionally, these iPS cell-derived NSCs are derived from adult cells, which bypass the sensitive ethical issue surrounding the use of human embryos, and since iPS cells are developed from a patient's own cells, the likelihood of immune rejection would be reduced.

Continued here:
Human neural stem cells with tumor targeting ability discovered

MEDIA RELEASE

IBN Discovers Human Neural Stem Cells with Tumor Targeting Ability A Promising Discovery for Breast Cancer Therapy

Singapore, April 20, 2012 Could engineered human stem cells hold the key to cancer survival? Scientists at the Institute of Bioengineering and Nanotechnology (IBN), the worlds first bioengineering and nanotechnology research institute, have discovered that neural stem cells possess the innate ability to target tumor cells outside the central nervous system. This finding, which was demonstrated successfully on breast cancer cells, was recently published in leading peer reviewed journal, Stem Cells.

A team of researchers led by IBN Group Leader, Dr Shu Wang, has made a landmark discovery that neural stem cells (NSCs) derived from human induced pluripotent stem (iPS) cells could be used to treat breast cancer. The effectiveness of using NSCs, which originate from the central nervous system, to treat brain tumors has been investigated in previous studies. This is the first study that demonstrates that iPS cell-derived NSCs could also target tumors outside the central nervous system, to treat both primary and secondary tumors.

To test the efficiency of NSCs in targeting and treating breast cancer, the researchers injected NSCs loaded with a suicide gene (herpes simplex virus thymidine) into mice bearing breast tumors. They did this using baculoviral vectors or gene carriers engineered from an insect virus (baculovirus), which does not replicate in human cells, making the carriers less harmful for clinical use. A prodrug (ganciclovir), which would activate the suicide gene to kill the cancerous cells upon contact, was subsequently injected into the mice. A dual-colored whole body imaging technology was then used to track the distribution and migration of the iPS-NSCs.

The imaging results revealed that the iPS-NSCs homed in on the breast tumors in the mice, and also accumulated in various organs infiltrated by the cancer cells such as the lung, stomach and bone. The survival of the tumor-bearing mice was prolonged from 34 days to 39 days. This data supports and explains how engineered iPS-NSCs are able to effectively seek out and inhibit tumor growth and proliferation.

Dr Shu Wang shared, We have demonstrated that tumor-targeting neural stem cells may be derived from human iPS cells, and that these cells may be used in combination with a therapeutic gene to cripple tumor growth. This is a significant finding for stem cell-based cancer therapy, and we will continue to improve and optimize our neural stem cell system by preventing any unwanted activation of the therapeutic gene in non-tumor regions and minimizing possible side effects.

IBNs expertise in generating human stem cells from iPS cells and our novel use of insect virus carriers for gene delivery have paved the way for the development of innovative stem cell-based therapies. With their two-pronged attack on tumors using genetically engineered neural stem cells, our researchers have discovered a promising alternative to conventional cancer treatment, added Professor Jackie. Y. Ying, IBN Executive Director.

Compared to collecting and expanding primary cells from individual patients, IBNs approach of using iPS cells to derive NSCs is less laborious and suitable for large-scale manufacture of uniform batches of cellular products for repeated patient treatments. Importantly, this approach will help eliminate variability in the quality of the cellular products, thus facilitating reliable comparative analysis of clinical outcomes.

Additionally, these iPS cell-derived NSCs are derived from adult cells, which bypass the sensitive ethical issue surrounding the use of human embryos, and since iPS cells are developed from a patients own cells, the likelihood of immune rejection would be reduced.

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:: 20, Apr 2012 :: IBN DISCOVERS HUMAN NEURAL STEM CELLS WITH TUMOR TARGETING ABILITY – A PROMISING DISCOVERY FOR ...

MADISON, Wis., March 28, 2012 /PRNewswire/ --Cellular Dynamics International, Inc. (CDI) today announced an expansion of its existing distribution agreement with iPS Academia Japan, Inc. to include iCell Neurons and iCell Endothelial Cells. The original distribution agreement, announced on June 8, 2011, covered the distribution of CDI's iCell Cardiomyocytes, the first commercially available product based on induced pluripotent stem cells (iPSCs), in Japan.

CDI is the world's largest manufacturer of human cellular tools for drug discovery and safety derived from iPSCs. The company currently manufactures iCell Cardiomyocytes, iCell Neurons and iCell Endothelial Cells with several other cell types, including liver cells, in development.

iPS Academia Japan was originally established to manage the patents and technology arising from the work of Shinya Yamanaka, MD, PhD of Kyoto University. CDI was the first foreign company granted a license to Yamanaka's iPSC patent portfolio by iPS Academia Japan, announced in May 2010.

"The reliability and consistent quality of CDI's cardiomyocytes have proven to be a valuable product offering to our academic and pharmaceutical customers," said Shosaku Murayama, President and CEO of iPS Academia Japan. "We're already seeing demand for additional human cell types manufactured by CDI by our Japanese customers."

Robert Palay, CEO and chairman of the board of CDI, noted, "We view the expansion of our distribution agreement with iPS Academia Japan as a vote of confidence in our ability to provide human iPSC-derived cells in the quantity, quality and purity required for scientists to realize the full potential of their experiments. We look forward to future growth of our relationship with iPS Academia Japan as we launch new human cell types and in vitro human disease models."

About Cellular Dynamics International Cellular Dynamics International, Inc. (CDI) is a leading developer of next-generation stem cell technologies for drug development, cell therapy, tissue engineering and organ regeneration. CDI harnesses its unique manufacturing technology to produce differentiated tissue cells from any individual's stem cell line in industrial quality, quantity and purity. CDI is accelerating the adoption of pluripotent stem cell technology, adapting its methods to fit into standard clinical practice by the creation of individual stem cell lines from a standard blood draw. CDI was founded in 2004 by Dr. James Thomson, a pioneer in human pluripotent stem cell research at the University of Wisconsin-Madison. CDI's facilities are located in Madison, Wisconsin. See http://www.cellulardynamics.com.

About iPS Academia Japan, Inc. iPS Academia Japan, Inc. (AJ) is an affiliate of Kyoto University, and its main role is, among other activities, to manage and utilize the patents and other intellectual properties held/controlled by Kyoto University and other universities in the field of iPSC technologies so that the research results contribute to health and welfare worldwide.

AJ was established in Kyoto in June 2008. AJ's patent portfolio consists of about 60 patent families (the total number of patent applications is about 220 cases) in the iPSC technology as of March 2012, and about 50 license arrangements have been executed with domestic or international enterprises. See http://ips-cell.net.

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Cellular Dynamics Expands Distribution Agreement with iPS Academia Japan, Inc. to Include Distribution of iCell ...

Editor's Choice Academic Journal Main Category: Diabetes Article Date: 13 Mar 2012 - 12:00 PDT

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1 (2 votes)

The study was carried out by Chutima Talchai, Ph.D, a New York Stem Cell Foundation-Druckenmiller Fellow, and Domenico Accili, M.D., professor of medicine at Columbia University Medical Center.

Type 1 diabetes is an autoimmune disease that kills cells in the pancreas which produce insulin, resulting in high levels of glucose in the blood. As the pancreas is unable to replace these cells, individuals suffering with the disease must inject insulin into themselves in order to manage their blood sugar. Patients must also monitor their sugar levels numerous times a day, as blood glucose that is too low or too high can be fatal.

For scientists researching type 1 diabetes, one of the leading goals is to replace lost insulin-producing cells with new cells that release insulin into the bloodstream as needed. Even though researchers are able to generate these cells in the laboratory from embryonic stem cells, they are not suitable for transplant in patients as they do not release insulin appropriately in response to sugar levels, potentially resulting in a deadly condition called hypoglycemia.

In the intestine of mice, the researchers found that certain gastrointestinal progenitor cells are able to generate insulin-producing cells.

Usually, progenitor cells are responsible for generating a vast range of cells, such as gastric inhibitory peptide, cells that produce serotonin, as well as other hormones secreted into the GI tract and bloodstream.

The researchers discovered that when they switched off Foxo1 (a gene known to contribute in cell fate decisions), the progenitor cells also generated cells that produced insulin. In addition, the team found that although more cells were produced when Foxo1 was switched off early in development, they were also produced when the Foxo1 was switched off in adult mice.

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Gut Cells Turned To Insulin Factories - New Type l Diabetes Treatment

Starting with the first-ever production of induced pluripotent stem cells (iPS cells) in 2006, cell reprogramming - the genetic conversion of cells from one type to another - has revolutionized stem cell research and opened the door to countless new medical applications. Inducing such reprogramming, however, is difficult, inefficient and time-consuming, involving a largely hit-or-miss process of selecting candidate genes.

In the current study, the OSC research team explored an alternative to iPS cells based on the use of transcriptional regulatory networks (TRNs), networks of transcription factors and the genes they regulate. Previous research by the team characterized the dynamic regulatory activities of such transcription factors during cellular differentiation from immature cell (monoblast) to developed (monocyte-like) cell using human acute monocytic leukemia cell lines (THP-1). Their findings led them to hypothesize that functional characteristics of the cell-type are maintained by its specific TRN.

Their new paper builds on this hypothesis, establishing a series of new methods for identifying transcription factors (TFs) for the monocyte network, which play a key role in inducing cell-specific functions. Four core TF genes of the monocyte TRN, identified using this approach, were introduced into human fibroblast cells, expression of which activated monocytic functions including phagocytosis, inflammatory response and chemotaxis. Genome-wide gene expression analysis of this reprogrammed cell showed monocyte-like gene expression profile, demonstrating that reconstruction of a functional TRN can be achieved by introducing core TRN elements into unrelated cell types.

Published in the journal PLoS ONE, the newly-developed methods open the door to a new form of direct cell reprogramming for clinical use which avoids the pitfalls of embryonic stem (ES) and induced pluripotent stem (iPS) cells, charting a course toward novel applications in regenerative medicine and drug discovery.

Provided by RIKEN (news : web)

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Study demonstrates cells can acquire new functions through transcriptional regulatory network

Published: March 12, 2012

(NEW YORK, NY, March 11, 2012) A study by Columbia researchers suggests that cells in the patients intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The researchconducted in micewas published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

Gut insulin cells express glucokinase, a key enzyme for glucose processing. Immunostaining detected insulin in red and glucokinase in green. Yellow marked merged colors.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai, who works in Dr. Accilis lab, is a New York Stem Cell Foundation-Druckenmiller Fellow.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Inactivation of Foxo1, a gene important for metabolism generated insulin producing cells in small intestines of newborn mice, as detected by immunofluorescence in red.Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisionsFoxo1the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients, Dr. Accili says.

Excerpt from:
Columbia Researchers Find Potential Role for Gut Cells in Treating Type I Diabetes

Public release date: 11-Mar-2012 [ | E-mail | Share ]

Contact: Karin Eskenazi ket2116@columbia.edu 212-342-0508 Columbia University Medical Center

NEW YORK, NY -- A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The researchconducted in micewas published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisionsFoxo1the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

"Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.

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A new approach to treating type I diabetes? Gut cells transformed into insulin factories

London, Mar 12 (ANI): A new study conducted by scientists suggests a new approach that could give patients the ability to make their own insulin-producing cells without a stem cell transplant.

Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose.

Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed.

Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels.

If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai and Domenico Accili from Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

They found that when they turned off a gene known to play a role in cell fate decisions-Foxo1-the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.

Excerpt from:
Gut cells transformed into insulin factories 'could help to treat type I diabetes'

ScienceDaily (Mar. 11, 2012) A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.

The research -- conducted in mice -- was published 11 March 2012 in the journal Nature Genetics.

Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.

A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.

The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.

The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.

Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisions -- Foxo1 -- the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood. "Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.

"Nobody would have predicted this result," Dr. Accili adds. "Many things could have happened after we knocked out Foxo1. In the pancreas, when we knock out Foxo1, nothing happens. So why does something happen in the gut? Why don't we get a cell that produces some other hormone? We don't yet know."

Insulin-producing cells in the gut would be hazardous if they did not release insulin in response to blood glucose levels. But the researchers say that the new intestinal cells have glucose-sensing receptors and do exactly that.

The insulin made by the gut cells also was released into the bloodstream, worked as well as normal insulin, and was made in sufficient quantity to nearly normalize blood glucose levels in otherwise diabetic mice.

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New approach to treating type 1 diabetes? Transforming gut cells into insulin factories

MADISON, Wis., March 8, 2012 /PRNewswire/ --Cellular Dynamics International, Inc. (CDI), the world's largest commercial producer of human induced pluripotent stem (iPS) cell lines and tissue cells for drug discovery and safety, today announced several customer presentations of studies employing the company's iCell products at the Society of Toxicology (SOT) Annual Meeting on March 11 to 15 in San Francisco. A number of these studies demonstrate the superior predictivity of CDI's human iPS cell-derived products compared to other cell models, such as animal models and immortalized cell lines, which are historically used in pharmaceutical drug discovery and toxicity testing.

Customers will present 11 abstracts employing CDI's human cells in their research during the SOT meeting. Several of these compare the superior ability of CDI's iCell Cardiomyocytes and iCell Hepatocytes to predict toxic responses to currently available cell models. Among them:

Puppala, D et al. (Abstract 420 Poster Board -642; Pfizer, Inc.) compared the ability of iCell Cardiomyocytes to a rat cardiac-derived cell line (H9C2) to predict the toxicity of 10 known in vivo cardiac toxins that were not flagged by the company's current in vitro assay systems. They found that iCell Cardiomyocytes showed increases in several toxicity signals and were more accurate in detecting cardiotoxicity than the rat cell line.

Guo, L et al. (Abstract 1168 Poster Board -433; Hoffman-La Roche) utilized sets of reference and internal compounds to determine the accuracy with which iCell Cardiomyocytes can predict arrhythmic effects. Based on drug-induced changes in beating pattern, iCell Cardiomyocytes correctly identified 17 of 19 reference compounds known to cause abnormal ECG patterns in humans and 17 of 17 internal compounds known to cause arrhythmia in non-rodent animals. These results demonstrate the predictive value of utilizing iCell Cardiomyocytes to identify proarrhythmic compounds.

Hong, S et al. (Abstract 1149 Poster Board -414; Bristol-Myers Squibb) evaluated the effects of three drug compounds using both iCell Cardiomyocytes and fetal rat cardiomyocytes utilizing multi-electrode array (MEA) assays. For all three compounds, iCell Cardiomyocytes were better suited than the fetal rat cardiomyocytes at predicting adverse in vivo effects, including those effects that were not discovered until small-scale clinical trials.

Kameoka, S et al. (Abstract 519 Poster Board -237; Hoffman-La Roche) compared the toxicity of three drug candidates previously tested on dog hepatocytes to iCell Hepatocytes and primary human hepatocytes. In dogs, two of the three compounds caused liver toxicity. The profiles of the two toxic compounds were almost identically recapitulated in vitro for both the primary human hepatocytes and iCell Hepatocytes. This study demonstrated that iCell Hepatocytes may be a valuable human model to predict hepatic toxicity in vitro.

Additional SOT presentations employing CDI's iCell products can be found on the SOT Annual Meeting website or at http://www.cellulardynamics.com/sot2012/posters.html.

"These studies are important contributors to the collective understanding that human in vitro cellular model systems are superior to animal models and immortalized cell lines when studying questions of human biology," said Chris Parker, chief commercial officer of CDI. "We recognize that iPS cell-derived tissues are a relatively new model for drug discovery and toxicity testing and must be validated and shown to be superior. It is gratifying that our pharmaceutical customers are presenting data validating the performance characteristics of our heart and liver cells in such an open scientific forum as the Society of Toxicology Annual Meeting. Third-party validation of iCell product performance coupled with CDI's proven ability to deliver human cells in the quantity, quality and purity required for pharmaceutical, biomedical and basic research positions us well for supplying customers with the human cells they need to improve healthcare."

About Cellular Dynamics International, Inc.Cellular Dynamics International, Inc. (CDI) is a leading developer of next-generation stem cell technologies for drug development, cell therapy, tissue engineering and organ regeneration. CDI harnesses its unique manufacturing technology to produce differentiated tissue cells from any individual's stem cell line in industrial quality, quantity and purity. CDI is accelerating the adoption of pluripotent stem cell technology, adapting its methods to fit into standard clinical practice by the creation of individual stem cell lines from a standard blood draw. CDI was founded in 2004 by Dr. James Thomson, a pioneer in human pluripotent stem cell research at the University of Wisconsin-Madison. CDI's facilities are located in Madison, Wisconsin. See http://www.cellulardynamics.com.

MEDIA CONTACTS:Joleen Rau Senior Director, Marketing & Communications Cellular Dynamics International, Inc. 608 310-5142 jrau@cellulardynamics.com

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Presentations at the Society of Toxicology Annual Meeting Demonstrate Superior Predictivity of Cellular Dynamics ...

Cambridge personalised medicines pioneer Horizon Discovery Ltd has landed another showpiece deal as part of a new super-cell consortium.

Business Weekly understands that the UK company stands to make a seven-figure haul over the lifetime of an EU-funded project aimed at understanding hES cell differentiation control.

Horizon provides research tools to support the development of personalised medicines. It has joined the EU-FP7 funded ‘4D-Cell-Fate’ consortium  whose aim is to shed light on how stem cell re-programming and differentiation is regulated at the epigenetic level.

As a member of the consortium, Horizon will generate cell-lines harbouring endogenous pathway reporter genes and labelled versions of specific epigenetic target proteins to study their function.

Commercialisation of the output of the programme will be governed by a consortium agreement defined by EU regulation.

4DCellFate brings together 12 groups from nine countries, including academics, research-intensive SMEs, and Pharma, each an international leader in its field, combining expertise in a wide range of cutting-edge technologies and scientific approaches.

The aim of the 4D CellFate project, which is currently funded for five years, is to establish an integrated approach to explore the structure and function of the large multi-protein epigenetic complexes that are involved in control of stem cell self-renewal, lineage commitment, and differentiation.

Horizon will use its proprietary virally-mediated gene-engineering technology, GENESIS™, to alter endogenous genes in hES cells (e.g. via tagging with GFP and HaloTag® technologies) with unprecedented accuracy and precision.

By gaining a greater insight into how Polycomb Repressive Complexes (PRCs), and Nucleosome Remodelling and Deacetylation complexes (NuRD) control stem cell differentiation, it is hoped that better methods will be identified to generate ethical sources of ‘iPS’ stem cells and direct the fate of stem cells into the many forms of specific tissue types that are needed for disease therapy.

Dr Chris Torrance, CSO of Horizon, said: “Generating stem cells and differentiated cell types with greater precision, definition and safety are key areas for delivering on the great promise that stem cell-based therapies could bring to many disease areas.

“Horizon’s gene targeting technology will play a key role in helping to dissect key biological pathways in the fate of stem cells as part of the 4D Cell Fate project. Through this process, new and important approaches to disease therapy will be determined.”

CEO Dr Darrin Disley added: “Our company has a commitment to active involvement in cutting-edge research with leading experts in translational fields, including bringing the power of rAAV-mediated gene targeting technology to the 4D Cell Fate project.”

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Horizon in new super-cell elite