Hepatocyte-like cells generated by direct reprogramming from murine somatic cells can repopulate decellularized livers

Biotechnol Bioeng. 2018 Nov;115(11):2807-2816. doi: 10.1002/bit.26784. Epub 2018 Sep 17.

Abstract

Direct reprogramming represents an easy technique to generate induced hepatocytes (iHeps) from somatic cells. However, current protocols are accompanied by several drawbacks as iHeps are heterogenous and lack fully mature phenotypes of primary hepatocytes. Here, we established a polycistronic expression system to induce the direct reprogramming of mouse embryonic fibroblasts towards hepatocytes. The resulting iHeps are homogenous and display key properties of primary hepatocytes, such as expression of hepatocyte markers, albumin secretion, and presence of liver transaminases. iHeps also possess the capacity to repopulate decellularized liver tissue and exhibit enhanced hepatic maturation. As such, we present a novel strategy to generate homogenous and functional iHeps for applications in tissue engineering and cell therapy.

Keywords: decellularized liver tissue; direct reprogramming; induced hepatocytes (iHeps); polycistronic expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Transplantation / methods*
  • Cellular Reprogramming Techniques / methods*
  • Fibroblasts / physiology*
  • Gene Expression Regulation
  • Hepatocytes / physiology*
  • Liver Diseases / therapy
  • Mice