title: Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats.
abstract: Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-β levels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γ levels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs.
authors: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
authors: Bin
authors: B
authors: Wu
authors: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China; Tianjin Key Laboratory of Organ Transplantation, Tianjin 300192, China.
authors: Hong-Li
authors: HL
authors: Song
authors: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, China.
authors: Yang
authors: Y
authors: Yang
authors: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, China.
authors: Ming-Li
authors: ML
authors: Yin
authors: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, China.
authors: Bo-Ya
authors: BY
authors: Zhang
authors: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, China.
authors: Yi
authors: Y
authors: Cao
authors: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
authors: Chong
authors: C
authors: Dong
authors: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
authors: Zhong-Yang
authors: ZY
authors: Shen