title: Umbilical cord-derived mesenchymal stem cells alleviate liver fibrosis in rats.
abstract: OBJECTIVE
  To evaluate the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation in the treatment of liver fibrosis.
  
  
  METHODS
  Cultured human UC-MSCs were isolated and transfused into rats with liver fibrosis induced by dimethylnitrosamine (DMN). The effects of UC-MSCs transfusion on liver fibrosis were then evaluated by histopathology; serum interleukin (IL)-4 and IL-10 levels were also measured. Furthermore, Kupffer cells (KCs) in fibrotic livers were isolated and cultured to analyze their phenotype. Moreover, UC-MSCs were co-cultured with KCs in vitro to assess the effects of UC-MSCs on KCs' phenotype, and IL-4 and IL-10 levels were measured in cell culture supernatants. Finally, UC-MSCs and KCs were cultured in the presence of IL-4 antibodies to block the effects of this cytokine, followed by phenotypical analysis of KCs.
  
  
  RESULTS
  UC-MSCs transfused into rats were recruited by the injured liver and alleviated liver fibrosis, increasing serum IL-4 and IL-10 levels. Interestingly, UC-MSCs promoted mobilization of KCs not only in fibrotic livers, but also in vitro. Co-culture of UC-MSCs with KCs resulted in increased production of IL-4 and IL-10. The addition of IL-4 antibodies into the co-culture system resulted in decreased KC mobilization.
  
  
  CONCLUSIONS
  UC-MSCs could increase IL-4 and promote mobilization of KCs both in vitro and in vivo, subsequently alleviating the liver fibrosis induced by DMN.
authors.affiliation: Ning-Li Chai, Xiao-Bin Zhang, En-Qiang Linghu, Department of Gastroenterology, PLA General Hospital, Beijing 100853, China.
authors.forename: Ning-Li
authors.initials: NL
authors.lastname: Chai
authors.affiliation: Ning-Li Chai, Xiao-Bin Zhang, En-Qiang Linghu, Department of Gastroenterology, PLA General Hospital, Beijing 100853, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Zhang
authors.affiliation: Ning-Li Chai, Xiao-Bin Zhang, En-Qiang Linghu, Department of Gastroenterology, PLA General Hospital, Beijing 100853, China.
authors.forename: Si-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Ning-Li Chai, Xiao-Bin Zhang, En-Qiang Linghu, Department of Gastroenterology, PLA General Hospital, Beijing 100853, China.
authors.forename: Ke-Xing
authors.initials: KX
authors.lastname: Fan
authors.affiliation: Ning-Li Chai, Xiao-Bin Zhang, En-Qiang Linghu, Department of Gastroenterology, PLA General Hospital, Beijing 100853, China.
authors.forename: En-Qiang
authors.initials: EQ
authors.lastname: Linghu
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D004128:Dimethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D016753:Interleukin-10; D015847:Interleukin-4; D004128:Dimethylnitrosamine
keywords: DMN; Dimethylnitrosamine; Interleukin-4; Kupffer cells; Liver fibrosis; Mesenchymal stem cells