Int. J. Mol. Sci. 2014, 15(4), 7004-7028; doi:10.3390/ijms15047004
Article

Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury

1email, 1email, 1email, 2email and 1,* email
Received: 5 March 2014; in revised form: 2 April 2014 / Accepted: 9 April 2014 / Published: 22 April 2014
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: 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 into 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 aspartate aminotransferase (AST) increased to similar levels irrespective of hMSC-HC transplantation. Yet, hMSC-HC resided in the damaged perivenous areas of the liver lobules short-term preventing apoptosis and thus progress of organ destruction. Disturbance of metabolic protein expression was lower in the livers receiving hMSC-HC. Seven weeks after APAP treatment, hepatic injury had completely recovered in groups both with and 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.
Keywords: cell transplantation; human mesenchymal stem cells; acute liver injury; stem cell-derived hepatocytes; hepatocyte differentiation
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MDPI and ACS Style

Stock, P.; Brückner, S.; Winkler, S.; Dollinger, M.M.; Christ, B. Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury. Int. J. Mol. Sci. 2014, 15, 7004-7028.

AMA Style

Stock P, Brückner S, Winkler S, Dollinger MM, Christ B. Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury. International Journal of Molecular Sciences. 2014; 15(4):7004-7028.

Chicago/Turabian Style

Stock, Peggy; Brückner, Sandra; Winkler, Sandra; Dollinger, Matthias M.; Christ, Bruno. 2014. "Human Bone Marrow Mesenchymal Stem Cell-Derived Hepatocytes Improve the Mouse Liver after Acute Acetaminophen Intoxication by Preventing Progress of Injury." Int. J. Mol. Sci. 15, no. 4: 7004-7028.

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