Bi-Potent Chemically Derived Hepatic Progenitors from Human Primary Hepatocytes Engraft and Function in Immunocompetent Mouse Liver


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Abstract

IntroductionRegenerative medicine is one of the most available and alternative breakthrough technologies to overcome the organ shortage problems for transplantation. In case of chronic liver diseases it is only useful cell therapy that hepatocytes-like cells is generated from patient fibroblasts by reprogramming into induced pluripotent stem cells, or direct converting. However, these cells are insufficient to regenerate of damaged liver.Materials and MethodsWe establish a stable induction method of patient specific hepatic progenitors from primary human hepatocytes using two independent small molecules.Results and DiscussionThree days of treatment with small molecules triggered expansion of small polygonal cells, which co-expressed known hepatic progenitor cells and lineage specific marker genes. These chemically derived human hepatic progenitor cells (hCdHs) could self-renew for at least 10 passages while retaining phenotype, normal karyotype and potential to differentiate into functional hepatocytes and biliary epithelial cells in vitro. A next-generation sequencing confirmed a high degree of molecular similarity between hCdHs and human hepatoblastsUpon intrasplenic transplantation into immunocompromised mice with a diseased liver, hCdHs effectively repopulated and restored damaged parenchyma without tumor formation.ConclusionIn conclusion, hCdHs provide a safe novel tool that permits expansion and genetic manipulation of patient-specific hepatic progenitor cells to study regeneration and repair of diseased liver.

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