Small molecule-mediated reprogramming of human hepatocytes into bipotent progenitor cells

Journal of Hepatology
Yohan KimDongho Choi

Abstract

Currently, much effort is directed towards the development of new cell sources for clinical therapy using cell fate conversion by small molecules. Direct lineage reprogramming to a progenitor state has been reported in terminally differentiated rodent hepatocytes, yet remains a challenge in human hepatocytes. Human hepatocytes were isolated from healthy and diseased donor livers and reprogrammed into progenitor cells by 2 small molecules, A83-01 and CHIR99021 (AC), in the presence of EGF and HGF. The stemness properties of human chemically derived hepatic progenitors (hCdHs) were tested by standard in vitro and in vivo assays and transcriptome profiling. We developed a robust culture system for generating hCdHs with therapeutic potential. The use of HGF proved to be an essential determinant of the fate conversion process. Based on functional evidence, activation of the HGF/MET signal transduction system collaborated with A83-01 and CHIR99021 to allow a rapid expansion of progenitor cells through the activation of the ERK pathway. hCdHs expressed hepatic progenitor markers and could self-renew for at least 10 passages while retaining a normal karyotype and potential to differentiate into functional hepatocytes and biliary epithe...Continue Reading

Citations

Feb 27, 2020·Expert Review of Gastroenterology & Hepatology·Minh Phuong NguyenAnil Dhawan
Jul 17, 2019·Inflammation and Regeneration·Tomoko YamaguchiTakahiro Ochiya
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Mar 19, 2020·Stem Cell Reviews and Reports·Guofang ChenXiaoping Wan
Feb 23, 2020·Experimental & Molecular Medicine·Yohan KimDongho Choi
Apr 2, 2020·British Journal of Cancer·Yu-Man TsuiIrene Oi-Lin Ng
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