输注供鼠骨髓间充质干细胞延长肾移植大鼠的存活时间

目的 探讨在同种大鼠肾移植中输注供者骨髓间充质干细胞(MSC)对急性排斥反应的影响以及延长受鼠存活时间的作用.方法 取Wistar大鼠骨髓,分离和培养其MSC.以Wistar 大鼠为供者,Lewis大鼠为受者,建立同种大鼠肾移植模型.根据受鼠处理方式的不同,分为低剂量MSC组、高剂量MSC组、CsA组及对照组,低剂量MSC组和高剂量MSC组于移植前后分别多次输注1×106个和t×107个供者MSC,CsA组于术后2d开始腹腔内注入CsA 0.5 mg·kg-1 ·d-1,以腹腔内注射PBS作为对照.移植后,比较各组受鼠的存活时间,观察各组移植肾功能及移植肾组织病理学改变.结果 低剂量MSC组、高剂量MSC组、CsA组及对照组受鼠的存活时间分别为(21.7±7.2)d、(31.2±14.3)d、(34.9±15.7)d及(9.0±2.3)d；低剂量MSC组、高剂量MSC组和CsA组存活时间均明显长于对照组(P＜0.01),而低剂量MSC组存活时间明显短于高剂量MSC组和CsA组(P＜0.05).术后第4天,高剂量MSC组和CsA组移植肾组织形态和结构基本正常；对照组移植肾组织则表现出典型的急性排斥反应,出现广泛间质性浸润,肾小管炎症和片状坏死、出血,肾小球炎症浸润严重；而与对照组相比,低剂量MSC组急性排斥反应的病理表现则要明显减轻.结论 同种肾移植大鼠输注供者MSC后,可以达到有效的免疫调节作用,并且可明显延长大鼠的存活时间,呈MSC剂量依赖性.

Mesenchymal stem cells modulate immune responses in a rat renal transplantation model

Objective To discuss the effect of mesenchymal stem cells (MSCs) in modulating immune responses in a rat renal transplantation model.Methods An in vivo trial of cytology was performed in one centre from March to December in 2008.Wistar rat donors and Lewis rat recipients in a renal transplantation model were randomly divided into 4 groups:MSCs (low dose,1 × 106 )therapy,MSCs (high dose,1 × 107) therapy,CsA monotherapy,and no therapy.Biochemistry methods were used to detect the levels of creatinine in serum.The survival time,renal grafting function and pathological changes of transplanted renal tissues were observed.Results Animal survival was significantly prolonged by MSCs (high dose) therapy and CsA monotherapy as compared with the no therapy group (both P＜0.01).Animal survival in the MSCs (low dose) therapy group was prolonged as compared with no therapy group (P＜0.01),but shortened as compared with MSCs (high dose) therapy group (P＜0.05) and CsA monotherapy group (P＜0.05).The MSCs (high dose) therapy and CsA therapy groups showed no special changes in histology,hut the control group showed acute rejection.Conclusion MSCs down-regulated immune responses,reduced production of some inflammatory mediators,preserved graft function in the initial stage after transplantation,and prolonged animal survival,and these effects were the same as those of CsA therapy with 1 × 107/day.