Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury |
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Authors: | Kyung-Ha Ryu So-Yeon Kim Ye-Ryung Kim So-Youn Woo Sun Hee Sung Han Su Kim Sung-Chul Jung Inho Jo Joo-Won Park |
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Affiliation: | 1. Department of Pediatrics, School of Medicine, Ewha Womans University, 911–1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea;2. Department of Biochemistry, School of Medicine, Ewha Womans University, 911–1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea;3. Department of Microbiology, School of Medicine, Ewha Womans University, 911–1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea;4. Department of Pathology, School of Medicine, Ewha Womans University, 911–1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea;5. 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;6. Department of Molecular Medicine, School of Medicine, Ewha Womans University, 911–1 Mok-Dong, Yang Cheon-Gu, Seoul 158-710, Republic of Korea;g 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 |
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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. |
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Keywords: | APAP, acetaminophen ALT, alanine aminotransferase AT, adipose tissue BM, bone marrow ConA, concanavalin A ELISA, enzyme-linked immunosorbent assay IL-2, interleukin-2 INF- γ, interferon-γ MSC, mesenchymal stem cell T-MSC, tonsil-derived mesenchymal stem cell TNF-α, tumor necrosis factor-α |
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