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

Peggy Stock¹  Sandra Br࿌kner¹  Sandra Winkler¹  Matthias M. Dollinger² 

[1] Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Applied Molecular Hepatology Laboratory, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig, Germany; E-Mails:;Clinics for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany; E-Mail:

关键词: cell transplantation;    human mesenchymal stem cells;    acute liver injury;    stem cell-derived hepatocytes;    hepatocyte differentiation;   

DOI  :  10.3390/ijms15047004

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland