title: Efficacy of adipose tissue-derived mesenchymal stem cells for fulminant hepatitis in mice induced by concanavalin A.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results suggest that ASC treatment has a high potential to be an innovative therapy for fulminant hepatitis.
authors.affiliation: Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Kubo
authors.forename: Shunji
authors.initials: S
authors.lastname: Narumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Soroku
authors.initials: S
authors.lastname: Yagihashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hakamada
authors.forename: Akio
authors.initials: A
authors.lastname: Nakane
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D003208:Concanavalin A; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase