Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

Yang, Yang; Song, Hong Li; Zhang, Wen; Wu, Ben Juan; Fu, Nan Nan; Dong, Chong; Shen, Zhongyang

doi:10.1186/s13287-016-0427-8

Cited by 21 publications

(33 citation statements)

References 71 publications

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“…Isolation, culture, and characterization of BMMSCs were performed according to previously described methods [24,27]. Briefly, BMMSCs were isolated from the femur and tibia of male SD rats and cultured in a cell culture incubator.…”

Section: Preparation and Identification Of Ho-1/bmmscsmentioning

confidence: 99%

“…However, BMMSC therapy has the disadvantage of insufficient migration to target organs and short survival time. Heme oxygenase 1 (HO-1), a potent cytoprotective enzyme, has been shown to exhibit antioxidant and antiapoptotic properties, reduce cell damage, regulate immunity, and prolong the survival time of BMMSCs and enhance their activity [24][25][26]. In this study, HO-1modified BMMSCs (HO-1/BMMSCs) were perfused into DCD liver grafts by NMP to increase the amount of BMMSCs in the target organ, thus enhancing their protective effect.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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Background: Donation after circulatory death (DCD) liver grafts have a poor prognosis after transplantation. We investigated whether the outcome of DCD donor organs can be improved by heme oxygenase 1 (HO-1)-modified bone marrow-derived mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP), and explored its underlying mechanisms. Methods: BMMSCs were isolated, cultured, and transduced with the HO-1 gene. An NMP system was established. DCD rat livers were obtained, preserved by different methods, and the recipients were divided into 5 groups: sham operation, static cold storage (SCS), NMP, BMMSCs combined with NMP, and HO-1/BMMSCs combined with NMP (HBP) groups. Rats were sacrificed at 1, 7, and 14 days after surgery; their blood and liver tissue samples were collected; and liver enzyme and cytokine levels, liver histology, high-mobility group box 1 (HMGB1) levels in monocytes and liver tissues, and expression of Toll-like receptor 4 (TLR4) pathway-related molecules were evaluated. Results: After liver transplantation, the SCS group showed significantly increased transaminase levels, liver tissue damage, and shorter survival time. The HBP group showed lower transaminase levels, intact liver morphology, prolonged survival time, and decreased serum and liver proinflammatory cytokine levels. In the NMP and SCS groups, HMGB1 expression in the serum, monocytes, and liver tissues and TLR4 pathway-related molecule expression were significantly decreased. Conclusions: HO-1/BMMSCs combined with NMP exerted protective effects on DCD donor liver and significantly improved recipient prognosis. The effect of HO-1/BMMSCs was greater than that of BMMSCs and was mediated via HMGB1 expression and TLR4 pathway inhibition.

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Section: Preparation and Identification Of Ho-1/bmmscsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

et al. 2020

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“…Furthermore, it is now evident that epithelial apoptosis is the mechanism of cell death in allograft rejection. [ 24 ] In the present study, less extensive cell apoptosis was found in the allograft after autologous ADSCs transplantation. Du et al .…”

Section: Discussionsupporting

confidence: 44%

Adipose-derived mesenchymal stem cells suppress of acute rejection in small bowel transplantation

Meng

Zhang

Chen

et al. 2017

Saudi J Gastroenterol

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Background/Aims:Adipose-derived mesenchymal stem cells (ADSCs) possess immunosuppressive activity and hold promise in autologous cell-based therapies. The aim of this study was to determine whether autologous ADSCs can improve outcomes in the rat small bowel transplantation (SBT) model.Materials and Methods:Allogeneic SBT followed by implantation of autologous ADSCs through the penile vein was conducted in Brown-Norway (BN) donor rats with Lewis (LEW) recipient rats infused with phosphate buffered solution as the control. Allograft and recipient peripheral blood were obtained. We assessed histopathology, apoptosis, cytokines, and regulatory T cells (Tregs). One-way analysis of variance was applied to assess the significance of the data.Results:It was found that ADSCs significantly reduced acute rejection and improved the allograft's survival rate. In addition, there were significantly fewer apoptotic cells in allograft mucosae in the ADSC group in comparison with the control group. Furthermore, levels of interleukin (IL)-10 and transforming growth factor-β1 were significantly elevated, whereas those of IL-2 and IL-17 levels were significantly reduced in the ADSC group when compared to the control group. Moreover, flow cytometry analysis revealed that there were significantly more peripheral Tregs after the infusion of ADSCs.Conclusions:These results demonstrate that implanted autologous ADSCs improve allogeneic small bowel allograft outcomes by attenuating the acute rejection and reducing inflammatory responses.

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“…The HITx has been used to establish the proof of concept of different immune modulation strategies to avoid rejection, as well as to study immunological reactions involved in graft rejection. 6 - 10 …”

mentioning

confidence: 99%

Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

Stringa

Romanin

Lausada

et al. 2017

Transplantation Direct

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Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats

Cited by 21 publications

References 71 publications

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

RETRACTED ARTICLE: Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts

Adipose-derived mesenchymal stem cells suppress of acute rejection in small bowel transplantation

Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

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