Z Gastroenterol 2016; 54(12): 1343-1404
DOI: 10.1055/s-0036-1597347
1. Fibrogenesis
Georg Thieme Verlag KG Stuttgart · New York

ABCB5+ mesenchymal stem cell transplantation in a chronic liver disease mouse model

VA Hartwig
1   University of Heidelberg, Medical Faculty Mannheim, Molecular Hepatology, Department of Medicine II, Mannheim, Germany
,
B Dewidar
1   University of Heidelberg, Medical Faculty Mannheim, Molecular Hepatology, Department of Medicine II, Mannheim, Germany
,
A Kluth
2   Rheacell GmbH, Heidelberg, Germany
,
N Tappenbeck
2   Rheacell GmbH, Heidelberg, Germany
,
A Dropmann
1   University of Heidelberg, Medical Faculty Mannheim, Molecular Hepatology, Department of Medicine II, Mannheim, Germany
,
C Meyer
1   University of Heidelberg, Medical Faculty Mannheim, Molecular Hepatology, Department of Medicine II, Mannheim, Germany
,
NM Meindl-Beinker
1   University of Heidelberg, Medical Faculty Mannheim, Molecular Hepatology, Department of Medicine II, Mannheim, Germany
,
S Dooley
1   University of Heidelberg, Medical Faculty Mannheim, Molecular Hepatology, Department of Medicine II, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2016 (online)

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Aim: ABCB5+ cells are mesenchymal stem cells isolated from human skin. Stem cells in general have the capacity to differentiate in any type of cell. Their therapeutic potential has already been shown by significantly reducing chronic venous ulcers and minimizing inflammation due to macrophage inhibition. Due to organ-donor limitations, stem cells provide a promising therapy option for patients with chronic/end stage liver disease since there is no other chance of survival than liver transplantation. In previous studies, little side effects in short time observations and no graft versus host effects have been monitored.

Methods: Mdr2-/- mice develop different stages of liver damage from fibrosis with inflammation to HCC. The mice were immunosuppressed by implanting an osmotic pump steadily releasing Tacrolimus. 24 hours post implantation, 5 × 105 ABCB5+ cells were injected into the tail vein. After two days, livers were resected to detect ABCB5+ cells in the liver, and after two and four weeks to measure any therapeutic effect in the damaged livers of Mdr2-/-mice. Changes or improvements of liver damage, in particular on inflammatory and fibrotic markers, were evaluated on mRNA level, tissue morphology and liver parameters in plasma.

Results: Application of ABCB5+ stem cells show no toxic effect on liver plasma parameters (ALT, AST) and a tendency of reduced alkaline phosphatase. Preliminary results indicate no obvious difference between untreated Mdr2-/- mice and stem cell transplanted animals after 2 and 4 weeks when analysing mRNA levels of fibrosis and inflammation markers. However, after two weeks of ABCB5+ treatment, there is a tendency of fibrosis and inflammation reduction, as analyzed by Sirius red and macrophage marker S100A4 staining, and after 2 weeks, this reduction is 4% lower than in controls, but after 4 weeks a 20% decrease.

Conclusions: The mice tolerated the ABCB5+ stem cells very well and we see a small beneficial effect, which will be further consolidated. An increasing cell number may help to approve the shown tendency and we do further analyses regarding fibrosis and progressed inflammation (e.g. hydroxyproline assay to quantify the collagen concentration).