Category Archives: Stem Cell Therapy

International Stem Cell Corporation Demonstrates Progress in the Use of Immune Matched Human Parthenogenetic Stem Cells to Promote the Development of Therapies for Diabetes and Liver Diseases

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, together with colleagues from ViaCyte (formerly Novocell), announced the successful derivation from its human parthenogenetic stem cells (hpSCs) of enriched cultures of definitive endoderm (DE). DE can be further developed into pancreas or liver cells. These new results create a platform for the development by ISCO of therapeutic products that have great potential to overcome the problem of rejection of transplanted cells by the patient's own immune system.

The results are described in a new article that will appear in Differentiation, the official journal of the International Society of Differentiation, published by Elsevier. The article concludes that, "Creation of the definitive endoderm lineages from hpSC represents the critical first step toward the development of hpSC-based cellular therapies for diseases of the liver or pancreas."

The article also describes improvement in an earlier published differentiation protocol. This new method extends ISCO's portfolio of intellectual property, demonstrating for the first time that the pre-treatment of undifferentiated cells by trichostatin A (TSA) significantly improves the efficacy of the differentiation procedure.

"This work represents a step forward in our ability to direct the differentiation of hpSCs to cell populations of sufficient purity for their eventual use to produce commercially viable populations of endoderm lineage cells such as liver and pancreas," said Nikolay Turovets, PhD, ISCO's Director of Research and Therapeutic Development, and the paper's co-author.

The published work was carried out in collaboration with scientists from ViaCyte, a leader in the direct differentiation of pluripotent stem cells toward definitive endoderm and pancreatic cells. The ViaCyte team was led by Dr. Baetge, currently Director of the Nestlé Institute of Health Sciences S.A., Lausanne, Switzerland, and Dr. D'Amour, ViaCyte's Director of Stem Cell Biology, both pioneers in the development of endoderm from human embryonic stem cells.

Andrey Semechkin, PhD, ISCO's CEO and the paper's co-author, said: "The fact that hpSC could be differentiated into progenitors of pancreatic and liver cells have now become a proven scientific fact. This data establishes hpSCs as a useful source of starting material in stem-cell based technologies and demonstrates excellent progress in therapeutic research."

According to earlier published scientific data, the most efficient method for deriving pancreatic and liver cells from human pluripotent stem cells is a method of direct differentiation that utilizes treatment of the stem cell cultures by specific signals directing differentiation toward particular lineages. Therefore it is extremely important that stem cells used for the differentiation process are able to respond to such signaling. Dr. Semechkin commented, "In this published paper we report for the first time that hpSCs can respond to well characterized differentiation signals. Moreover, we demonstrate that these unique cells respond to similar signaling factors and demonstrate gene expression dynamics and transitions that simulate properties of DE differentiation during vertebrate development and closely follow differentiation of human embryonic stem cells to DE. These data are extremely important as they demonstrate that hpSCs have therapeutic potential; however, parthenogenetic stem cells have an additional benefit of superior immune-matching capabilities and don't pose the same ethical questions associated with embryonic stem cells."

The Abstract of the paper is available on the Elsevier web site. The title of the paper is: "Human parthenogenetic stem cells produce enriched populations of definitive endoderm cells after trichostatin A pretreatment."

Full text article can be obtained upon request to corresponding author, Nikolay Turovets, PhD: nturovets@intlstemcell.com.

Additional information regarding ISCO's therapeutic projects is available on the ISCO website:http://www.internationalstemcell.com/therapeutics.htm.

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB):

International Stem Cell Corporation is a California-based biotechnology company focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell™, while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated technological developments and potential therapeutic applications, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
or
Nikolay Turovets, PhD
nturovets@intlstemcell.com

Neural Tumor-Initiating Cells Have Distinct Telomere Maintenance and Can be Safely Targeted for Telomerase Inhibition by Pedro Castelo-Branco and 12 co-authors, including Uri Tabori, Clin Cancer Res 2011(Jan 1); 17(1): 111-121 [Full text]. Translational Relevance:

Pediatric neural tumors (brain tumors and neuroblastoma) are the leading cause of morbidity and mortality in childhood cancer. This is due to their ability to recur after minimal disease is achieved. Telomerase is active in most malignant pediatric neural tumors. Therefore, telomerase inhibition may offer an effective treatment option for such patients. Because normal stem cells may require telomerase for continuous self-renewal, this therapy may have devastating effects on normal nervous system development and maintenance.

This study reveals that telomerase activation exists only in the tumor-initiating cancer subpopulation and is critical to sustain their survival and self-renewal potential. Importantly, normal neural or neural crest stem cells do not require telomerase for their self-renewal. Furthermore, as opposed to conventional chemoradiation therapies, telomerase inhibition results in irreversible loss of self-renewal capacity of tumor initiating cells in vitro and in vivo.

These observations uncover a difference between normal and cancer stem cell biology in the nervous system and suggest that telomerase inhibition may offer a specific and safe therapeutic approach for these devastating tumors.

For a commentary on this article, see: Anita B Hjelmeland and Jeremy N Rich, Clin Cancer Res 2011(Jan 1); 17(1): 3-5 (unlike the article, the commentary is not publicly accessible). Abstract:

Telomerase is an important mechanism by which cancers escape replicative senescence. In neural tumors, cancer stem cells express telomerase, suggesting that this may explain their preferential tumorigenesis. Oligonucleotide telomerase targeting selectively disrupts cancer stem cell growth through the induction of differentiation, adding to the armamentarium of anticancer stem cell therapies.

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, applauds a recent announcement by researchers at Nationwide Children's Hospital showing the use of parthenogenetic stem cells as a potential strategy to treat genetic diseases such as Huntington's disease, beta thalassemia or tuberous sclerosis.

In a scientific paper entitled, "Gene therapy by allele selection in a mouse model of beta-thalassemia" recently published in the Journal of Clinical Investigation, a team of researchers from the Center for Molecular and Human Genetics (NationwideChildren's Hospital, Columbus, OH), the University of Pennsylvania, the University of North Carolina and the University of Minnesota led by John McLaughlin Ph.D., describe how they used a mouse model of an inherited blood disorder to show that parthenogenesis could be used to create "genetically clean" stem cells. These parthenogenetic stem cells demonstrated the ability to correct certain symptoms of such a disease.

Dr. Andrey Semechkin, CEO of ISCO, commented, "We at ISCO are particularly pleased to note this animal model research into the potential of parthenogenetic stem cells since ISCO has created method for creating immortal human parthenogenetic stem cell (hpSC) lines. We are constantly seeking ways to use such technology to treat human diseases, and this announcement is a positive indication showing the potential of parthenogenetic stem cells to treat certain types of autosomal dominant diseases such as particular forms of beta thalassemia or even Huntington's disease. We expect that the transition from animal models to human therapy using parthenogenetic cells will continue to evolve as ISCO continues to conduct its own therapeutic research and to collaborate with researchers across the world to discover new ways to use parthenogenesis and parthenogenetic stem cells to cure human disease. We have great hope that animal research such as that just reported will open new doors to human therapy and look forward to making our human parthenogentic lines available for such therapies."

ISCO created and patented the first proven technology to create human parthenogenetic stem cell lines from unfertilized human eggs. This technology has similar potential advantages as those described in the work done at Nationwide Children's Hospital; i.e., the creation of human parthenogenetic stem cells that could eliminate a defective copy of a gene and can be immune-matched to the egg donor. ISCO's technology has the additional ethical advantage of not harming a viable human embryo.

Dr Semechkin continues, "ISCO is actively conducting research on the creation and application of differentiated derivatives of hpSC for therapeutic use. Specifically, ISCO has initiated a number of pre-clinical animal studies utilizing both hepatocytes and separately retina pigment epithelium cells, derived from hpSC. ISCO's scientists were also the first to demonstrate the ability of hpSC to differentiate into neural cells and to develop approaches to obtain stable lines of parthenogenetic neural cells. These achievements open up the opportunity to assess the efficacy and safety of using parthenogenetic stem cells as a source to create neural cells for the treatment of diseases such as Parkinson's, Alzheimer's, and other neurodegenerative disorders. The work presented by Dr. McLaughlin once again confirms ISCO's unique position in the field of stem cell based therapies."

The work done by Dr. McLaughlin can be found at: http://www.jci.org/articles/view/45377?search%5Barticle_text%5D=&search%5Bauthors_text%5D=mclaughlin.

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB):

International Stem Cell Corporation is a California-based biotechnology company focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell™, while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated technological developments and therapeutic applications, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
or
Jeffrey Janus, Senior Vice President
760-940-6383
jjanus@intlstemcell.com

International Stem Cell Corporation (OTCBB:ISCO), http://www.internationalstemcell.com, announced today that its Chairman, Kenneth Aldrich and the CEO of its Lifeline Skin Care subsidiary, Ruslan Semechkin, PhD, will present a Webinar discussion of the State of the Company and its plans for its Skin Care subsidiary on Wednesday, January 19, 2011 at 10:00 a.m. PST. In announcing the event, Mr. Aldrich stressed that its purpose is not to announce any new programs or financial results, but to attempt to provide an overview of events during the past year and offer shareholders a perspective on what to expect in the coming year. The dial-in number for participants is: 1 (800) 588-4973. Please provide the confirmation number 28808144 to the operator upon calling in. An alternate dial-in number is 1 (847) 230-5643. The confirmation number will be the same for both numbers. A replay of the call will be available on the home page of the company's website at:http://www.internationalstemcell.com.

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB):

International Stem Cell Corporation is a California-based biotechnology company focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell™, while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

Key Words: Stem Cells, Biotechnology, Parthenogenesis

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
760-940-6383
kaldrich@intlstemcell.com
or
Ruslan Semechkin, PhD,
Vice President, ISCO, CEO Lifeline Skin Care
ras@intlstemcell.com

Neural Tumor-Initiating Cells Have Distinct Telomere Maintenance and Can be Safely Targeted for Telomerase Inhibition by Pedro Castelo-Branco and 12 co-authors, including Uri Tabori, Clin Cancer Res 2011(Jan 1); 17(1): 111-121 [Full text]. Translational Relevance:

Pediatric neural tumors (brain tumors and neuroblastoma) are the leading cause of morbidity and mortality in childhood cancer. This is due to their ability to recur after minimal disease is achieved. Telomerase is active in most malignant pediatric neural tumors. Therefore, telomerase inhibition may offer an effective treatment option for such patients. Because normal stem cells may require telomerase for continuous self-renewal, this therapy may have devastating effects on normal nervous system development and maintenance.

This study reveals that telomerase activation exists only in the tumor-initiating cancer subpopulation and is critical to sustain their survival and self-renewal potential. Importantly, normal neural or neural crest stem cells do not require telomerase for their self-renewal. Furthermore, as opposed to conventional chemoradiation therapies, telomerase inhibition results in irreversible loss of self-renewal capacity of tumor initiating cells in vitro and in vivo.

These observations uncover a difference between normal and cancer stem cell biology in the nervous system and suggest that telomerase inhibition may offer a specific and safe therapeutic approach for these devastating tumors.

For a commentary on this article, see: Anita B Hjelmeland and Jeremy N Rich, Clin Cancer Res 2011(Jan 1); 17(1): 3-5 (unlike the article, the commentary is not publicly accessible). Abstract:

Telomerase is an important mechanism by which cancers escape replicative senescence. In neural tumors, cancer stem cells express telomerase, suggesting that this may explain their preferential tumorigenesis. Oligonucleotide telomerase targeting selectively disrupts cancer stem cell growth through the induction of differentiation, adding to the armamentarium of anticancer stem cell therapies.