Assessment of the hepatocytic differentiation ability of human skin-derived ABCB5 + stem cells

Exp Cell Res. 2018 Aug 15;369(2):335-347. doi: 10.1016/j.yexcr.2018.05.040. Epub 2018 Jun 1.

Abstract

The continuously decreasing willingness for liver donation aggravates treatment of end-stage liver diseases requiring organ transplantation as the only curative strategy. Cell therapy approaches using human hepatocytes or stem cell-derived hepatocyte-like cells may be a therapeutic option out of this dilemma. ABCB5-positive mesenchymal stromal cells from human skin featured promising potential to treat immune-mediated diseases. Since most of chronic liver diseases involve exaggerating immune mechanisms, it was the aim to demonstrate in this study, whether ABCB5+ stem cells may serve as a resource to generate hepatocytic cells for application in liver cell transplantation. Using an established single-step protocol, which had been successfully applied to differentiate mesenchymal stromal cells into the hepatocytic lineage, ABCB5+ skin-derived stem cells did not gain significant characteristics of hepatocytes. Yet, upon culture in hepatocytic differentiation medium, ABCB5+ stem cells secreted immunomodulatory and anti-fibrotic factors as well as proteins, which may prompt hepatic morphogenesis besides others. Hepatic transplantation of ABCB5+ stem cells, which had been prior cultured in hepatocytic differentiation medium, did not cause any obvious deterioration of liver architecture suggesting their safe application. Thus, human ABCB5+ skin-derived stem cells secreted putative hepatotropic factors after culture in hepatocytic differentiation medium.

Keywords: ABCB5; Cell therapy; Hepatic transplantation; Liver injury; Stem cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Cell Culture Techniques / methods
  • Cell Differentiation / physiology
  • Cell Lineage
  • Culture Media
  • Hepatectomy
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism*
  • Hepatocytes / transplantation
  • Humans
  • Liver Regeneration
  • Liver Transplantation
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Skin / cytology*
  • Skin / metabolism*
  • Transplants / cytology
  • Transplants / metabolism

Substances

  • ABCB5 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biomarkers
  • Culture Media