Abstract
Fulminant hepatitis is mainly caused by excessive immune response-mediated liver injury and its definitive therapy is liver transplantation. Mesenchymal stem cells, one of the adult stem cells, have an immunomodulatory effect on immune cells and reside in various tissues. The aim of this study was to investigate a therapeutic effect of adipose tissue-derived mesenchymal stem cells (ASCs) on fulminant hepatitis induced by concanavalin A (ConA). The ASCs were isolated from adipose tissues of BALB/c mice and confirmed by detection of cell surface markers and induction of multi-lineage differentiation. BALB/c mice were injected with ConA and treated with ASCs, phosphate buffered saline (PBS) or splenocytes (SPLCs). Survival rates, levels of serum liver enzymes, titers of serum cytokines, histopathology and localization of ASCs were investigated. The survival rate of ASC-injected mice significantly increased compared to PBS or SPLC-injected mice. This effect was dependent on doses and timing of ASCs injected. Improvement of liver enzyme levels, histopathological changes and suppression of inflammatory cytokine production were observed in ASC-injected mice. Fluorescent stained ASCs were detected in inflammatory liver, but not in normal liver. These results suggest that ASC treatment has a high potential to be an innovative therapy for fulminant hepatitis.
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