title: Immunomodulatory effects of bone marrow mesenchymal stem cells overexpressing heme oxygenase-1: Protective effects on acute rejection following reduced-size liver transplantation in a rat model.
abstract: Here we explore the T-lymphocyte suppressive and immunomodulatory effects of bone marrow mesenchymal stem cells (BMMSCs) overexpressing heme oxygenase-1 (HO-1) on acute rejection following reduced-size liver transplantation (RLT) in a rat model. The proliferation activity, cell cycle progression, secretion of proinflammatory cytokines, expression of CD25 and CD71 in lymphocytes, and activity of NK cells were found to be significantly lowered, and the proportion of regulatory T cells (Tregs) was found to be increased relative to BMMSCs when Adv-HO-1/BMMSCs were co-cultured with Con A ex vivo; secretion of anti-inflammatory cytokines was significantly higher. When treated with saline, BMMSCs or Adv-HO-1/BMMSCs, post-transplantation rats receiving Adv-HO-1/BMMSCs showed better median survival time, lower rejection activity index, higher anti-inflammatory cytokine levels, lower proinflammatory cytokine levels, more peripheral Tregs, and lower natural killer cell viability. These results suggest that HO-1 enhanced and prolonged the effects of BMMSCs on acute rejection following RLT, with immunomodulatory effects in which adaptive and innate immunity, as well as paracrine signaling, may play important roles.
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China.
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Shen
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China; Key Laboratory of Emergency and Care Medicine of Ministry of Health, Tianjin 300192, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China; Key Laboratory of Emergency and Care Medicine of Ministry of Health, Tianjin 300192, PR China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Yin
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Emergency and Care Medicine of Ministry of Health, Tianjin 300192, PR China.
authors.forename: Bo-Ya
authors.initials: BY
authors.lastname: Zhang
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, PR China; Tianjin Key Laboratory of Organ Transplantation, Tianjin 300192, PR China. Electronic address: hlsong26@163.com.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Song
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D056747:Immunomodulation; D016031:Liver Transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058408:Th1-Th2 Balance; D058504:Th17 Cells / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
chemical_list: D051547:Heme Oxygenase-1
keywords: BM MSCS; HO-1; Immunomodulation; Liver transplantation; Rejection