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Efficient programming of human mesenchymal stem cell‐derived hepatocytes by epigenetic regulations
Author(s) -
Tsai WeiLun,
Yeh PoHung,
Tsai ChiaYun,
Ting ChinTsung,
Chiu YenHui,
Tao MiHua,
Li WanChun,
Hung ShihChieh
Publication year - 2017
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13451
Subject(s) - mesenchymal stem cell , cd81 , hepatocyte , trichostatin a , cancer research , stem cell , microbiology and biotechnology , biology , histone deacetylase , in vitro , medicine , hepatitis c virus , immunology , histone , biochemistry , virus , gene
Background and Aim In view of its unique properties of detoxification and involvement of metabolic and biochemical functions, in vitro hepatocyte culture serves as a valuable material for drug screening and mechanistic analysis for pathology of liver diseases. The restriction of rapid de‐differentiation and inaccessibility of human hepatocytes from routine clinical procedure, however, limits its use. Methods To address this issue, the effort to direct human mesenchymal stem cells (hMSCs) into hepatocytes using a modified protocol was proposed. With the additional treatment of histone deacetylase inhibitor (HDACi) and DNA methyltransferase inhibitor (DNMTi), in vitro hMSC‐derived hepatocytes were cultivated and their hepatic characteristics were examined. Results By using a modified protocol, it was shown that Trichostatin A and 5‐aza‐2‐deoxycitidine protected differentiating cells from death and could sufficiently trigger a wide range of liver‐specific markers as well as liver functions including albumin production, glycogen storage, and urea cycle in hMSC‐derived hepatocytes. The increased mRNA expression for hepatitis C virus (HCV) entry including CD81, Occludin, LDL receptor, and scavenger receptor class B type I in hMSC‐derived hepatocytes was also detected, implying its potential to be utilized as an in vitro model to analyze dynamic HCV infection. Conclusions The present study successfully established a protocol to direct hMSCs into hepatocyte‐like cells suggesting the beneficial impact to apply HDACi and DNMTi as potent modulators for hMSCs to liver differentiation.