International Stem Cell Corporation (OTCBB:ISCOE) announces the discovery of a novel, patent-pending technology to produce unlimited numbers of liver cells (hepatocytes) that are free of contamination with potentially dangerous undifferentiated cells. The technology is based on the natural, physiological properties of the cellular environment, and does not require any additional purification of the final product. The starting materials for the production are pluripotent stem cells, either ISCO's proprietary human parthenogenetic stem cells (hpSCs) or human embryonic stem cells (hESCs).


The technology is described in a new article that will appear in Cell Transplantation, the Regenerative Medicine Journal (currently the article is available only in electronic form). The published data also reinforce that hpSCs can provide the cellular material necessary for the implementation of cell-based therapies.


Marie Csete, M.D., Ph.D., co-author of the paper, said, "Derivation of differentiated cell products that are not contaminated with undifferentiated cells solves a major technical roadblock in the development of all pluripotent stem cell-based therapies because undifferentiated stem cells with tumorigenic potential can persist through long differentiation protocols. Therefore methods to generate pure differentiated cells for transplantation are critical for creating successful cell therapies. Furthermore, the elegant technology developed by ISCO scientists to enforce critical steps in differentiation illustrates the power and importance of basic engineering tools in stem cell biology."


Nikolay Turovets, Ph.D., Director of Research and Therapeutic Development at ISCO and co-author of the paper stated, "The technology discovered by our research team is based on reproducing features of the normal human embryonic microenvironment. The method uses a differentiation device that incorporates a three-dimensional extracellular matrix, combined with a porous membrane. Treatment of undifferentiated cells above the membrane using differentiation-directed proteins results in permitting the desired cells to migrate through the membrane into the matrix, where they further differentiate into functional hepatocytes."


Jeffrey Fair, M.D., liver transplant surgeon and Director of Translational Research for the Cedars-Sinai Comprehensive Transplant Center and Department of Surgery in Los Angeles, and co-author of the paper said, "Derivatives of HLA-homozygous hpSCs are likely to be significantly less susceptible to immune rejection after transplantation, thus offering major advantages over other pluripotent cell sources of hepatocytes. In the paper, we demonstrated that hepatocytes derived from hpSCs in this differentiation system demonstrate activities that are missing in a number of metabolic liver diseases, such as expression of AAT and OTC genes. Thus, personalized HLA-matching, as well as presence of the required activities make the pure hepatocyte population derived from hpSCs an attractive development candidate for cell therapy of metabolic liver diseases, urea cycle disorders, AAT-deficiency or other liver diseases in which a single hepatocyte product can ameliorate disease."


The approach used to derive a pure hepatocyte population is a technology platform that may allow derivation of various cell populations from different sources.


Andrey Semechkin, Ph.D., President and CEO of ISCO, and co-author of the paper stated, "We have discovered technology that has a number of features and advantages, and our plans are to expand the applications of this platform to develop new products. This system is universal and does not depend of the particularities of cell lines. As such it could be successfully used with hpSCs, hESCs and, we believe, with induced pluripotent stem cells (iPSs). Because isolation of undifferentiated cells happens at the first step of the differentiation procedure, the technology could be used to isolate other cell types, for example pancreatic or heart cells. Also, because technology is based on a natural process, cell separation is accomplished without any cell damage, in contrast to physical purification methods such as FACS, or magnetic sorting."


An electronic pre-copy-edited version of the paper entitled "Derivation of high-purity definitive endoderm from human parthenogenetic stem cells using an in vitro analog of the primitive streak" is available at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/ct0284agapova.


A color version of the paper will be available when the print publication is issued. Prior to print publication, color figures can be obtained upon request from Nikolay Turovets, PhD:nturovets@intlstemcell.com.


About International Stem Cell Corporation
International Stem Cell Corporation is 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 the 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 genders, ages and racial background. This offers the potential to create the first true stem cell bank, UniStemCell™. 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 http://www.internationalstemcell.com.
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Forward-looking Statements
Statements pertaining to anticipated developments, the potential production and benefits of stem cell lines, the potential applications and benefits of the new technology, 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 and new technologies, 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 forward-looking statements.

International Stem Cell Corporation
760-940-6383
Kenneth C. Aldrich
Chairman
kaldrich@intlstemcell.com
or
Nikolay Turovets, Ph.D.
Director of Research and Therapeutic Development
nturovets@intlstemcell.com
or:
Lippert/Heilshorn & Associates
Don Markley (dmarkley@lhai.com)
310-691-7100