Effects of transplanted bone-marrow-derived mesenchymal stem cells in animal models of acute hepatitis

• Published in: Cell and tissue research Vol. 351; no. 3; pp. 477 - 486
• Main Authors: Zhu, Xishan, He, Baoxin, Zhou, Xinna, Ren, Jun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.03.2013; Springer; Springer Nature B.V
• Subjects: Acute Disease; Allografts; Analysis; animal models; Animals; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Concanavalin A; Culture Media, Conditioned - pharmacology; Cytokines - metabolism; Cytoprotection - drug effects; Disease Models, Animal; Female; Health aspects; Hepatitis; Hepatitis - pathology; Hepatitis - therapy; Human Genetics; Humans; Hydrogen Peroxide - pharmacology; Inflammation - pathology; Inflammation Mediators - metabolism; intravenous injection; liver; Liver - drug effects; Liver - pathology; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mice; Mice, Inbred C57BL; Molecular Medicine; Natural Killer T-Cells - metabolism; Proteomics; recruitment; Regular Article; Stem cells; therapeutics; Toy industry; Transplantation; Hepatitis; Natural killer T cells; Immunoregulation; Cellular therapy; Immune regulation; Differentiation; Mouse (C57bl/6); Mesenchymal stem cells
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-012-1524-3

Our aim was to evaluate the therapeutic effects of bone-marrow-derived mesenchymal stem cells (BMMSCs) on ConA-induced hepatitis and to elucidate the possible mechanism involved. MSCs were isolated from bone marrow and their characteristics and anti-apoptotic effects on the L02 cell line were analyzed. The effect of intravenous infusion of BMMSCs on liver damage was also tested. Furthermore, the recruitment of donor BMMSCs to the liver of recipient animals and their effects on the activity of intrahepatic natural killer T (NKT) cells were investigated. BMMSCs ameliorated liver damage in a time- and dose-dependent manner. Donor BMMSCs were detected in the livers of recipient animals, suggesting that tissue damage stimulated the migration of BMMSCs. Transplanted BMMSCs also suppressed the activity of intrahepatic NKT cells, not only in the liver but throughout the body. The general infusion of BMMSCS ameliorated immunoregulatory activities by the suppression of intrahepatic NKT cells.