title: Reduction of acute rejection by bone marrow mesenchymal stem cells during rat small bowel transplantation.
abstract: BACKGROUND
  Bone marrow mesenchymal stem cells (BMMSCs) have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats.
  
  
  METHODS
  Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control), isogeneically transplanted rats (BN-BN) and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point.
  
  
  RESULTS
  Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ while upregulating IL-10 and transforming growth factor (TGF)-β expression and increasing Treg levels.
  
  
  CONCLUSIONS
  BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation.
authors.affiliation: Tianjin First Central Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Song
authors.affiliation: Tianjin First Central Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Tianjin First Central Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Ben-Juan
authors.initials: BJ
authors.lastname: Wu
authors.affiliation: Tianjin First Central Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Nan-Nan
authors.initials: NN
authors.lastname: Fu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zheng
authors.forename: Chong
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Don
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008297:Male; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D014185:Transplantation, Isogeneic
chemical_list: D016207:Cytokines