Rapid and high-efficiency generation of mature functional hepatocyte-like cells from adipose-derived stem cells by a three-step protocol

Stem Cell Res Ther. 2015 Oct 5:6:193. doi: 10.1186/s13287-015-0181-3.

Abstract

The generation of functional hepatocytes is a major challenge for regenerative medicine and drug discovery. Here we show a method that facilitates generation of induced functional hepatocytes (iHeps) from adipose-derived stem cells (ADSCs) within 9 days. iHeps express hepatocytic gene programs and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity. Upon transplantation into mice with carbon tetrachloride (CCl4)-induced acute fulminant liver failure, iHeps restore the liver function and prolong survival. The work could contribute to the development of alternative strategies to obtain nonhepatic cell-derived mature hepatocytes with potential for biomedical and pharmaceutical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / cytology
  • Adult Stem Cells / physiology*
  • Animals
  • Carbon Tetrachloride
  • Cell Differentiation*
  • Cells, Cultured
  • Female
  • Hepatocytes / physiology*
  • Hepatocytes / transplantation
  • Liver Failure / chemically induced
  • Liver Failure / therapy
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Rats, Inbred Lew

Substances

  • Carbon Tetrachloride