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...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2016-01-01
|
Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2016/9235073 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832558267696414720 |
---|---|
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. |
format | Article |
id | doaj-art-b5e5a2731a614b8f875c0f699309ceb1 |
institution | Kabale University |
issn | 1687-966X 1687-9678 |
language | English |
publishDate | 2016-01-01 |
publisher | Wiley |
record_format | Article |
series | Stem Cells International |
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 |
work_keys_str_mv | AT binwu improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT honglisong improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT yangyang improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT mingliyin improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT boyazhang improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT yicao improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT chongdong improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats AT zhongyangshen improvementoflivertransplantationoutcomebyhemeoxygenase1transducedbonemarrowmesenchymalstemcellsinrats |