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

Area of Science:

• Stem cell biology
• Hepatology
• Drug discovery

Background:

• In vitro hepatocyte cultures are crucial for drug screening and liver disease research.
• Challenges include rapid cell de-differentiation and limited access to human hepatocytes.

Purpose of the Study:

• To establish a protocol for differentiating human mesenchymal stem cells (hMSCs) into functional hepatocytes.
• To investigate the role of specific inhibitors in enhancing this differentiation process.

Main Methods:

• Utilized a modified protocol to direct hMSC differentiation.
• Incorporated histone deacetylase inhibitor (HDACi) and DNA methyltransferase inhibitor (DNMTi) treatments.
• Cultivated and examined hepatic characteristics of the resulting hMSC-derived hepatocytes.

Main Results:

• HDACi and DNMTi protected differentiating cells and induced liver-specific markers and functions (albumin production, glycogen storage, urea cycle).
• hMSC-derived hepatocytes showed increased expression of genes essential for hepatitis C virus (HCV) entry.
• Demonstrated potential as an in vitro model for dynamic HCV infection studies.

Conclusions:

• Successfully established a protocol for differentiating hMSCs into hepatocyte-like cells.
• HDACi and DNMTi act as potent modulators for hMSC liver differentiation.
• This approach offers a promising avenue for generating functional hepatocytes for research and therapeutic applications.