title: Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury.
abstract: Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease.
authors: Department of Pediatrics, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea; Department of Ewha Global Top 5 Research Program, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul158-710, Republic of Korea.
authors: Kyung-Ha
authors: KH
authors: Ryu
authors: Department of Biochemistry, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea.
authors: So-Yeon
authors: SY
authors: Kim
authors: Department of Biochemistry, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea.
authors: Ye-Ryung
authors: YR
authors: Kim
authors: Department of Microbiology, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea.
authors: So-Youn
authors: SY
authors: Woo
authors: Department of Pathology, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea.
authors: Sun Hee
authors: SH
authors: Sung
authors: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea; Department of Ewha Global Top 5 Research Program, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul158-710, Republic of Korea.
authors: Han Su
authors: HS
authors: Kim
authors: Department of Biochemistry, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea.
authors: Sung-Chul
authors: SC
authors: Jung
authors: Department of Molecular Medicine, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea; Department of Ewha Global Top 5 Research Program, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul158-710, Republic of Korea.
authors: Inho
authors: I
authors: Jo
authors: Department of Biochemistry, School of Medicine, Ewha Womans University, 911-1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea. Electronic address: joowon.park@ewha.ac.kr.
authors: Joo-Won
authors: JW
authors: Park
mesh_terms: D000328:Adult; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003208:Concanavalin A / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D037483:Galectin 1 / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000633:toxicity*; D014066:Palatine Tonsil; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D037483:Galectin 1; D008934:Mitogens; D012333:RNA, Messenger; D003208:Concanavalin A
keywords: Galectin; Immune; Liver; Mesenchymal stem cell; Tonsil