Postdoc The University of Hong Kong, China (People's Republic)
Abstract: The generation of functional human hepatocytes on a large scale is crucial for advancements in cell therapy and drug development. However, primary hepatocytes face challenges such as donor scarcity, unstable in vitro cultures, and genetic variability. The direct differentiation of human pluripotent stem cells into hepatocytes presents a promising avenue for regenerative medicine. In this study, we successfully generated hepatocyte-like cells (HLCs) from human expanded potential stem cells (hEPSCs) by replicating the developmental processes of the liver. These hEPSC-derived HLCs closely resembled primary hepatocytes in morphology, expressed specific hepatic markers at both transcriptional and protein levels, and exhibited essential liver functions, including albumin production. Notably, treatment with the THRB ligand T3 enhanced the expression of CYP3A4, a vital liver metabolism enzyme and a marker of mature hepatocytes, in hEPSC-HLCs. When transplanted into mice afflicted with metabolic liver disease stemming from fumarylacetoacetate dehydrolase (Fah) deficiency, hEPSC-derived HLCs not only restored liver function but also prolonged survival.
Funding Source: The Innovation and Technology Commission
