Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats

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. Or...

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Main Authors: Bin Wu, Hong-Li Song, Yang Yang, Ming-Li Yin, Bo-Ya Zhang, Yi Cao, Chong Dong, Zhong-Yang Shen
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/9235073
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author Bin Wu
Hong-Li Song
Yang Yang
Ming-Li Yin
Bo-Ya Zhang
Yi Cao
Chong Dong
Zhong-Yang Shen
author_facet Bin Wu
Hong-Li Song
Yang Yang
Ming-Li Yin
Bo-Ya Zhang
Yi Cao
Chong Dong
Zhong-Yang Shen
author_sort Bin Wu
collection DOAJ
description 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.
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spelling doaj-art-b5e5a2731a614b8f875c0f699309ceb12025-02-03T01:32:46ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/92350739235073Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in RatsBin Wu0Hong-Li Song1Yang Yang2Ming-Li Yin3Bo-Ya Zhang4Yi Cao5Chong Dong6Zhong-Yang Shen7Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, ChinaDepartment of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, ChinaTianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, ChinaTianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, ChinaTianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, ChinaTianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, ChinaDepartment of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, ChinaDepartment of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, ChinaBone 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.http://dx.doi.org/10.1155/2016/9235073
spellingShingle Bin Wu
Hong-Li Song
Yang Yang
Ming-Li Yin
Bo-Ya Zhang
Yi Cao
Chong Dong
Zhong-Yang Shen
Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats
Stem Cells International
title Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats
title_full Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats
title_fullStr Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats
title_full_unstemmed Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats
title_short Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats
title_sort improvement of liver transplantation outcome by heme oxygenase 1 transduced bone marrow mesenchymal stem cells in rats
url http://dx.doi.org/10.1155/2016/9235073
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