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Attenuation of the Inflammatory Response After Acetaminophen‐Induced Injury by Human Mesenchymal Stem Cell‐Derived Hepatocytes in Mice
Author(s) -
Stock Peggy,
Brückner Sandra,
Winkler Sandra,
Dollinger Matthias,
Christ Bruno
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.416.3
Subject(s) - mesenchymal stem cell , hepatocyte , liver injury , stem cell , acetaminophen , transplantation , bone marrow , in vivo , inflammation , lobules of liver , liver regeneration , regeneration (biology) , chemistry , in vitro , pharmacology , biology , medicine , immunology , microbiology and biotechnology , pathology , biochemistry
Mesenchymal stem cells from human bone marrow (hMSC) have the potential to differentiate into hepatocyte‐like cells in vitro and continue to maintain important hepatocyte functions in vivo after transplantation into host mouse livers. Here, hMSC were differentiated to hepatocyte‐like cells in vitro (hMSC‐HC) and transplanted into livers of immunodeficient Pfp/Rag2 ‐/‐ mice treated with a sublethal dose of acetaminophen (APAP) to induce acute liver injury. APAP induced a time‐ and dose‐dependent damage of perivenous areas of the liver lobule. Serum levels of AST increased to similar levels irrespective of hMSC‐HC were transplanted or not. Yet, hMSC‐HC were found in the damaged perivenous areas of the liver lobules short‐term preventing apoptosis and thus gross destruction of the organ. Disturbance of metabolic and secretory protein expression was lower in the livers receiving hMSC‐HC. 7 weeks after APAP treatment, hepatic injury had completely recovered in groups both, with or without hMSC‐HC. Clusters of transplanted cells appeared predominantly in the periportal portion of the liver lobule and secreted human albumin featuring a prominent quality of differentiated hepatocytes. Thus, hMSC‐HC attenuated the inflammatory response and supported liver regeneration after acute injury induced by acetaminophen. They hence may serve as a novel source of hepatocyte‐like cells suitable for cell therapy of acute liver diseases.