HDAC inhibitors support long-term expansion of porcine hepatocytes in vitro

Biomed Pharmacother. 2024 Aug:177:116973. doi: 10.1016/j.biopha.2024.116973. Epub 2024 Jun 21.

Abstract

Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.

Keywords: Gene manipulation; Histone deacetylase inhibitors; Long-term proliferation; Microencapsulation; Porcine hepatocytes.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Hepatocytes* / drug effects
  • Histone Deacetylase Inhibitors* / pharmacology
  • Mice
  • Stem Cells / drug effects
  • Swine

Substances

  • Histone Deacetylase Inhibitors