chir-99021 and Liver-Failure

Hepatocytes have been successfully generated from human pluripotent stem cells (hPSCs). However, the cost-effective and clinical-grade generation of hepatocytes from hPSCs still need to be improved. In this study, we reported the production of functional hepatocytes from clinical-grade human embryonic stem cells (hESCs) under good manufacturing practice (GMP) requirements. We sequentially generated primitive streak (PS), definitive endoderm (DE), hepatoblasts and hepatocyte-like cells (HLCs) from hESCs in the different stages with completely defined reagents. During hepatoblast differentiation, dimethyl sulfoxide (DMSO), transferrin, L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (Vc-Mg), insulin, and sodium selenite were used instead of cytokines and FBS/KOSR. Then, hepatoblasts were differentiated into HLCs that had a typical hepatocyte morphology and possessed characteristics of mature hepatocytes, such as metabolic-related gene expression, albumin secretion, fat accumulation, glycogen storage, and inducible cytochrome P450 activity in vitro. HLCs integrated into the livers of Tet-uPA Rag2

Topics: Activins; Animals; Cell Culture Techniques; Cell Differentiation; Culture Media; Cytochrome P-450 Enzyme System; DNA-Binding Proteins; Endoderm; Gene Expression Regulation, Developmental; Hepatocytes; Human Embryonic Stem Cells; Humans; Interleukin Receptor Common gamma Subunit; Liver; Liver Failure; Liver Regeneration; Male; Mice; Mice, Knockout; Multigene Family; Pyridines; Pyrimidines; Stem Cell Transplantation; Transcriptome