Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model.
Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver.
Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany. Electronic address: sandra.pelz@medizin.uni-leipzig.de.
Sandra
S
Winkler
Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen, Germany. Electronic address: ekamphorst@ukaachen.de.
Erawan
E
Borkham-Kamphorst
Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany. Electronic address: peggy.stock@medizin.uni-leipzig.de.
Peggy
P
Stock
Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany. Electronic address: sandra.brueckner@medizin.uni-leipzig.de.
Sandra
S
Brückner
Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany. Electronic address: matthias.dollinger@uniklinik-ulm.de.
Matthias
M
Dollinger
Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen, Germany. Electronic address: rweiskirchen@ukaachen.de.
Ralf
R
Weiskirchen
Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany; Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig, Germany. Electronic address: bruno.christ@medizin.uni-leipzig.de.
Bruno
B
Christ
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D022781:Hepatocytes / Q000473:pathology; D064593:Heterografts; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides
Hepatocyte; Immune-deficient mouse; Mesenchymal stem cells; Non-alcoholic steatohepatitis; Stem cell differentiation; Stem cell therapy