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  • International Stem Cell Corp. (ISCO) Poster Selected For Presentation At American Association For The Study Of Liver Diseases Meeting 0 comments
    Dec 2, 2013 6:09 PM | about stocks: ISCO

    The American Association for the Study of Liver Diseases (AASLD) recently highlighted International Stem Cell's presentation, titled "Human parthenogenetic stem cell-derived hepatocyte transplantation controls serum bilirubin in Gunn rats," as a Presidential Poster of Distinction at The Liver Meeting during the four-day AASLD'S 64th Annual Meeting in Washington, D.C.

    The presentation authors are Dr. Alina Ostrowska, Dr. Larisa Agapova, Tiffany Chu, Dr. Trudy Christiansen-Weber and Dr. Ruslan Semechkin, all of which are from International Stem Cell.

    International Stem Cell is a development stage biotech company focused on therapeutic applications of human stem cells as well as the development and commercialization of cell-based biomedical products. The company was the first to develop and perfect a new class of human stem cells, called parthenogenetic stem cells, created from unfertilized human eggs. In addition to its therapeutic focus, International Stem Cell also provides a growing revenue stream through two wholly owned subsidiaries.

    AASLD presented the following information on the company's liver program:

    Background: Extensive studies indicate that pluripotent stem cells are a highly promising alternative source of histocompatible cells for cell replacement therapy. Hepatocyte-like cells (HLCs) derived from human parthenogenetic stem cells (hpSCs) might be transplanted to treat a wide array of metabolic liver diseases including CN1 (Crigler-Najjar syndrome type I). CN1 is the paradigm of inherited liver-based metabolic disorders in that the host liver is lacking one hepatic enzyme - UGT1A1, which is essential for the conjugation and excretion of bilirubin. To obtain ultimate proof that differentiation has been achieved, following the preliminary evaluation in vitro, we tested hepatocyte-like cells in vivo using an accurate animal model of CN1, the Gunn rats which accumulate toxic plasma levels of unconjugated bilirubin.

    Methods: Highly enriched populations of definitive endoderm were generated from hpSCs in a novel 3D-differentiation system and then induced to differentiate towards HLCs. The final cells were characterized by using expression profiling including RT-qPCR for dynamic expression of the hepatic lineage genes, immunohistochemistry and FACS analysis to demonstrate hepatocyte-specific markers, drug metabolism assays to determine the activity of CYP450s as well as a luminescent method for measuring UGT activity profile. Production of liver-specific proteins in the culture medium was simultaneously measured by quantitative ELISA. To evaluate engraftment and functional repopulation in vivo, CFSE-labeled hpHC were injected (10×106 per animal) into the spleen of 4-6 week old Gunn rats. Blood serum samples of tested animals were evaluated for indirect bilirubin levels 4, 8 and 19 weeks post-transplantation. Liver tissue samples were embedded in OCT compound and snap frozen, until cryosectioning.

    Results: CFSE-labeled HLCs transferred into the spleen were shown to migrate into the liver. Multiple engrafted cells were observed in the periportal regions of the liver lobules and formed morphologically distinct aggregates. The overall liver structure appeared undamaged without signs of inflammation, fibrosis or tumor. Significant decrease and long-term stabilization of bilirubin levels was demonstrated in the serum of tested animals in comparison with sham-treated controls. Although by week 19th serum indirect bilirubin was not normalized in transplanted animals, it resulted in an average 70% reduction compared with pretreatment levels.

    Conclusion: This pre-clinical study describes important supportive evidence of the potential efficacy and safety of hpSC-derived hepatocytes which might constitute an easily available source to obtain a large number of transplantable cells for regenerative treatments of CN1. In the long-term, experience with HLCs transplantation for CN1 can be used to develop therapeutic strategies for more common inherited liver diseases.

    For more information, visit internationalstemcell.com

    QualityStocks provides investor relations services to publicly traded companies in exchange for compensation. This article may be part of our efforts to widen a client's exposure. To read our full disclaimer, visit http://disclaimer.qualitystocks.net

    Stocks: ISCO
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