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

Journal Article · Wed Aug 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.05.040· OSTI ID:23082680

Tietze, Lysann; Winkler, Sandra; Hempel, Madlen ^[1]; Kluth, Mark Andreas ^[2]; Tappenbeck, Nils ^[2]; Ganss, Christoph ^[2]; Dooley, Steven ^[3]; Christ, Bruno ^[1]

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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)
3. Department of Medicine II, Molecular Hepatology Section, Medical Faculty Mannheim, University of Heidelberg, Mannheim (Germany)

Highlights: • Stem cell-derived hepatocytes may be used for cell therapy of liver diseases. • ABCB5-positive stem cell feature characteristics of mesenchymal stromal cells. • Hepatocytic differentiation of ABCB5{sup +} stem cells is incomplete. • However, they secrete hepatotropic factors that may support liver regeneration. • Hepatic delivery of the cells does not cause obvious adverse effects in the mouse. 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{sup +} 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{sup +} skin-derived stem cells did not gain significant characteristics of hepatocytes. Yet, upon culture in hepatocytic differentiation medium, ABCB5{sup +} stem cells secreted immunomodulatory and anti-fibrotic factors as well as proteins, which may prompt hepatic morphogenesis besides others. Hepatic transplantation of ABCB5{sup +} 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{sup +} skin-derived stem cells secreted putative hepatotropic factors after culture in hepatocytic differentiation medium.

• OSTI ID: 23082680
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 369; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL DIFFERENTIATION
LIVER CELLS
MICE
MORPHOGENESIS
SKIN
STEM CELLS