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Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

Abstract:

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.

24786317

Projects: C4: Disturbance of liver lobule organization in NAFLD, C6: Organization and function of the sinusoidal system and the liver lob..., G: Clinical translation, Showcase Steatosis

Exp. Cell Res.
Exp. Cell Res. :
3rd May 2014

Sandra Winkler, Erawan Borkham-Kamphorst, Peggy Stock, Sandra Brückner, Matthias Dollinger, Ralf Weiskirchen, Bruno Christ

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[Sandra Brückner] [Bruno Christ] [Karl Winkler]

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Cell and Liver
Views: 1407
  • Created: 19th May 2014 at 20:13

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