Details

Autor(en) / Beteiligte

• Tsai, Wei-Lun
• Yeh, Po-Hung
• Tsai, Chia-Yun
• Ting, Chin-Tsung
• Chiu, Yen-Hui
• Tao, Mi-Hua
• Li, Wan-Chun
• Hung, Shih-Chieh

Titel

Efficient programming of human mesenchymal stem cell-derived hepatocytes by epigenetic regulations

Ist Teil von

• Journal of gastroenterology and hepatology, 2017-01, Vol.32 (1), p.261-269

Ort / Verlag

Australia: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. 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. 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. 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.