AIM To investigate whether bone marrow mesenchymal stem cells(BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection.METHODS Lewis rat BMMSCs wer...AIM To investigate whether bone marrow mesenchymal stem cells(BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection.METHODS Lewis rat BMMSCs were cultured in vitro. Thirdpassage BMMSCs were transduced with the CXCR3/HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to smallbowel transplant. Six time points(instant, 1 d, 3 d, 7 d, 10 d, and 14 d)(n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines.RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group(53 d) was significantly longer than that of the HO-1 modified BMMSCs group(39 d), the BMMSCs group(26 d), and the NS group(control group)(16 d)(P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3/HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased(P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-γ, and TNF-α levels were significantly decreased and the levels of IL-10 and TGF-β were significantly increased(P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.展开更多
一、前言
器官移植是目前治疗终末期脏器功能衰竭最为有效的手段。研究表明,供器官获取、保存及移植后缺血再灌注损伤是影响移植预后的重要因素。自20世纪中期起,各研究中心不断研发、改进器官保护液,Collins液、UW液(the University ...一、前言
器官移植是目前治疗终末期脏器功能衰竭最为有效的手段。研究表明,供器官获取、保存及移植后缺血再灌注损伤是影响移植预后的重要因素。自20世纪中期起,各研究中心不断研发、改进器官保护液,Collins液、UW液(the University of Wisconsin solution,UW)、HTK(histidine-tryptophan-ketoglutarate solution)液等相继问世,促进了基于器官保护液的静态冷保存(static cold storage,scs)技术的迅速发展,使器官保存进一步摆脱了时间及地域限制,器官保护技术进入崭新的纪元,极大推动了器官移植事业的进步。展开更多
基金Supported by The National Natural Science Foundation of China,No.81670574,No.81441022 and No.81270528The Natural Science Foundation of Tianjin,China,No.08JCYBJC08400,No.11JCZDJC27800 and No.12JCZDJC25200The Technology Foundation of the Health Bureau of Tianjin,China,No.2011KY11
文摘AIM To investigate whether bone marrow mesenchymal stem cells(BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection.METHODS Lewis rat BMMSCs were cultured in vitro. Thirdpassage BMMSCs were transduced with the CXCR3/HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to smallbowel transplant. Six time points(instant, 1 d, 3 d, 7 d, 10 d, and 14 d)(n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines.RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group(53 d) was significantly longer than that of the HO-1 modified BMMSCs group(39 d), the BMMSCs group(26 d), and the NS group(control group)(16 d)(P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3/HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased(P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-γ, and TNF-α levels were significantly decreased and the levels of IL-10 and TGF-β were significantly increased(P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.
文摘一、前言
器官移植是目前治疗终末期脏器功能衰竭最为有效的手段。研究表明,供器官获取、保存及移植后缺血再灌注损伤是影响移植预后的重要因素。自20世纪中期起,各研究中心不断研发、改进器官保护液,Collins液、UW液(the University of Wisconsin solution,UW)、HTK(histidine-tryptophan-ketoglutarate solution)液等相继问世,促进了基于器官保护液的静态冷保存(static cold storage,scs)技术的迅速发展,使器官保存进一步摆脱了时间及地域限制,器官保护技术进入崭新的纪元,极大推动了器官移植事业的进步。