给予供体来源的间充质干细胞可延长大鼠心脏移植异体移植物的存活时间。
Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft.
作者信息
Zhou H P, Yi D H, Yu S Q, Sun G C, Cui Q, Zhu H L, Liu J C, Zhang J Z, Wu T J
机构信息
Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an City, Shannxi Province, China.
出版信息
Transplant Proc. 2006 Nov;38(9):3046-51. doi: 10.1016/j.transproceed.2006.10.002.
BACKGROUND
Mesenchymal stem cells (MSCs) are multipotent adult elements that have recently been shown to have profound immunomodulatory effects both in vitro and in vivo. Herein we have examined the impact of intravenous infusion of donor MSCs on the survival of transplanted hearts in a rat allograft model.
METHODS
Recipient Fisher344 rats were transplanted with hearts from inbred Wistar rats. Wistar rat MSCs were infused via the tail vein at designated intervals. In vitro mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays were performed to assess whether MSCs downregulated T-cell responses in vivo. Real-time polymerase chain reaction (PCR) was used to analyze the Th1/Th2 balance in MSC-treated and control groups.
RESULTS
The MSCs cultured in vitro exhibited multipotential for differentiation. Survival of the allografts was markedly prolonged by administration of MSCs compared with the controls, namely mean survivals of 12.4 vs 6.4 days, respectively. Real-time PCR showed a shift in the Th1/Th2 balance toward Th2. By MLR and CML assays, untreated control rats showed greater alloreactivity than did MSC-treated rats.
CONCLUSION
Our results indicated that MSCs suppressed allogeneic T-cell responses both in vitro and in vivo. Intravenous administration of MSCs prolonged the survival of transplanted hearts, possibly by induction of allograft tolerance through changing the Th1/Th2 balance.
背景
间充质干细胞（MSCs）是多能成体细胞成分，最近研究表明其在体外和体内均具有显著的免疫调节作用。在此，我们研究了在大鼠同种异体移植模型中静脉输注供体间充质干细胞对移植心脏存活的影响。
方法
将近交系Wistar大鼠的心脏移植给受体Fisher344大鼠。在指定时间间隔经尾静脉输注Wistar大鼠间充质干细胞。进行体外混合淋巴细胞反应（MLR）和细胞介导的淋巴细胞溶解（CML）试验，以评估间充质干细胞是否在体内下调T细胞反应。采用实时聚合酶链反应（PCR）分析间充质干细胞处理组和对照组的Th1/Th2平衡。
结果
体外培养的间充质干细胞表现出多向分化潜能。与对照组相比，间充质干细胞给药显著延长了同种异体移植物的存活时间，即平均存活时间分别为12.4天和6.4天。实时PCR显示Th1/Th2平衡向Th2偏移。通过MLR和CML试验，未处理的对照大鼠比间充质干细胞处理的大鼠表现出更强的同种异体反应性。
结论
我们的结果表明，间充质干细胞在体外和体内均抑制同种异体T细胞反应。静脉注射间充质干细胞延长了移植心脏的存活时间，可能是通过改变Th1/Th2平衡诱导同种异体移植物耐受来实现的。
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