HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal st...

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Autores principales:	Huan Cao, Longlong Wu, Xuan Tian, Weiping Zheng, Mengshu Yuan, Xiang Li, Xiaorong Tian, Yuxin Wang, Hongli Song, Zhongyang Shen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Acute rejection Bone marrow mesenchymal stem cells Natural killer T cells Liver transplantation Normothermic machine perfusion Medicine (General) R5-920 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/126e95313a5c4daba01f9732d00975ce
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spelling	oai:doaj.org-article:126e95313a5c4daba01f9732d00975ce2021-11-28T12:06:25ZHO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats10.1186/s13287-021-02647-51757-6512https://doaj.org/article/126e95313a5c4daba01f9732d00975ce2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13287-021-02647-5https://doaj.org/toc/1757-6512Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.Huan CaoLonglong WuXuan TianWeiping ZhengMengshu YuanXiang LiXiaorong TianYuxin WangHongli SongZhongyang ShenBMCarticleAcute rejectionBone marrow mesenchymal stem cellsNatural killer T cellsLiver transplantationNormothermic machine perfusionMedicine (General)R5-920BiochemistryQD415-436ENStem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acute rejection Bone marrow mesenchymal stem cells Natural killer T cells Liver transplantation Normothermic machine perfusion Medicine (General) R5-920 Biochemistry QD415-436
spellingShingle	Acute rejection Bone marrow mesenchymal stem cells Natural killer T cells Liver transplantation Normothermic machine perfusion Medicine (General) R5-920 Biochemistry QD415-436 Huan Cao Longlong Wu Xuan Tian Weiping Zheng Mengshu Yuan Xiang Li Xiaorong Tian Yuxin Wang Hongli Song Zhongyang Shen HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats
description	Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.
format	article
author	Huan Cao Longlong Wu Xuan Tian Weiping Zheng Mengshu Yuan Xiang Li Xiaorong Tian Yuxin Wang Hongli Song Zhongyang Shen
author_facet	Huan Cao Longlong Wu Xuan Tian Weiping Zheng Mengshu Yuan Xiang Li Xiaorong Tian Yuxin Wang Hongli Song Zhongyang Shen
author_sort	Huan Cao
title	HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats
title_short	HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats
title_full	HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats
title_fullStr	HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats
title_full_unstemmed	HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats
title_sort	ho-1/bmmsc perfusion using a normothermic machine perfusion system reduces the acute rejection of dcd liver transplantation by regulating nkt cell co-inhibitory receptors in rats
publisher	BMC
publishDate	2021
url	https://doaj.org/article/126e95313a5c4daba01f9732d00975ce
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HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

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