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

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

Author information

1
Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Applied Molecular Hepatology, University of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany.
2
RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 069120 Heidelberg, Germany; TICEBA GmbH, Im Neuenheimer Feld 517, 069120 Heidelberg, Germany.
3
RHEACELL GmbH & Co. KG, Im Neuenheimer Feld 517, 069120 Heidelberg, Germany.
4
Department of Medicine II, Molecular Hepatology Section, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
5
Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Applied Molecular Hepatology, University of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany. Electronic address: bruno.christ@medizin.uni-leipzig.de.

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

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