title: Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats.
abstract: We determined whether bone marrow mesenchymal stem cells (BMMSCs) transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective factor, could improve outcomes for small bowel transplantation (SBTx) in rats.
  
  
  
  We performed heterotopic SBTx from Brown Norway rats to Lewis rats, before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs, BMMSCs, and normal saline served as controls. The animals were sacrificed after 1, 5, 7, or 10 days. At each time point, we measured small bowel histology and apoptosis, HO-1 protein and mRNA expression, natural killer (NK) cell activity, cytokine concentrations in serum and intestinal graft, and levels of regulatory T (Treg) cells.
  
  
  
  The saline-treated control group showed aggravated acute cellular rejection over time, with mucosal destruction, increased apoptosis, NK cell activation, and upregulation of proinflammatory and immune-related mediators. Both the Ad/BMMSC-treated group and the BMMSC-treated group exhibited attenuated acute cellular rejection at an early stage, but the effects receded 7 days after transplantation. Strikingly, the Ad/HO-1/BMMSC-treated group demonstrated significantly attenuated acute cellular rejection, reduced apoptosis and NK cell activity, and suppressed concentrations of inflammation and immune-related cytokines, and upregulated expression of anti-inflammatory cytokine mediators and increased Treg cell levels.
  
  
  
  Our data suggest that Ad/HO-1-transduced BMMSCs have a reinforced effect on reducing acute rejection and protecting the outcome of SBTx in rats.
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China. hlsong26@163.com.|Tianjin Key Laboratory of Organ Transplantation, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China. hlsong26@163.com.
authors.forename: Hong Li
authors.initials: HL
authors.lastname: Song
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
authors.forename: Ben Juan
authors.initials: BJ
authors.lastname: Wu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
authors.forename: Nan Nan
authors.initials: NN
authors.lastname: Fu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China. shenzhy@tmu.edu.cn.
authors.forename: Zhong Yang
authors.initials: ZY
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism*; D006085:Graft Survival / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051547:Heme Oxygenase-1
keywords: Acute cellular rejection; Bone marrow mesenchymal stem cells; Heme oxygenase-1; Small bowel transplantation