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."
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