title: Tonsil-derived mesenchymal stem cells ameliorate CCl4-induced liver fibrosis in mice via autophagy activation.
abstract: Liver transplantation is the treatment of choice for chronic liver failure, although it is complicated by donor shortage, surgery-related complications, and immunological rejection. Cell transplantation is an alternative, minimally invasive treatment option with potentially fewer complications. We used human palatine tonsil as a novel source of mesenchymal stem cells (T-MSCs) and examined their ability to differentiate into hepatocyte-like cells in vivo and in vitro. Carbon tetrachloride (CCl4) mouse model was used to investigate the ability of T-MSCs to home to the site of liver injury. T-MSCs were only detected in the damaged liver, suggesting that they are disease-responsive. Differentiation of T-MSCs into hepatocyte-like cells was confirmed in vitro as determined by expression of hepatocyte markers. Next, we showed resolution of liver fibrosis by T-MSCs via reduction of TGF-β expression and collagen deposition in the liver. We hypothesized that autophagy activation was a possible mechanism for T-MSC-mediated liver recovery. In this report, we demonstrate for the first time that T-MSCs can differentiate into hepatocyte-like cells and ameliorate liver fibrosis via autophagy activation and down-regulation of TGF-β. These findings suggest that T-MSCs could be used as a novel source for stem cell therapy targeting liver diseases.
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: Minhwa
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: Yu-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: Yeonsil
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 1] Department of Otorhinolaryngology-Head and Neck Surgery, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea [2] Ewha Global Top 5 Research Program.
authors.forename: Han Su
authors.initials: HS
authors.lastname: Kim
authors.affiliation: 1] Department of Molecular Medicine, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea [2] Ewha Global Top 5 Research Program.
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Park
authors.affiliation: 1] Department of Molecular Medicine, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea [2] Ewha Global Top 5 Research Program.
authors.forename: Inho
authors.initials: I
authors.lastname: Jo
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea.
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
authors.affiliation: 1] Department of Pharmaceutics, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 120-750, Korea [2] Ewha Global Top 5 Research Program.
authors.forename: Hyukjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: 1] Department of Chemistry and Nano Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul, 120-750, Korea [2] Ewha Global Top 5 Research Program.
authors.forename: Byeongmoon
authors.initials: B
authors.lastname: Jeong
authors.affiliation: 1] Department of Pediatrics, Ewha Womans University School of Medicine, 1071 Anyangcheon-ro Yangcheon-gu, Seoul, 158-710, Korea [2] Ewha Global Top 5 Research Program.
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D001343:Autophagy; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL; D014066:Palatine Tonsil / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D016212:Transforming Growth Factor beta; D002251:Carbon Tetrachloride