人脐带间充质干细胞应用于肝移植患者的观察

Clinical application of human umbilical cord-derived mesenchymal stem cells in liver transplantation patients

背景:近年来间充质干细胞的免疫调节作用可被应用于诱导机体免疫耐受研究。目的:评估脐带间充质干细胞应用于肝移植患者的安全性和可行性。方法:培养人脐带间充质干细胞并进行鉴定。经医学伦理委员会同意后,将总计50例患者经1∶1的比例按入组时间随机分入试验组和对照组,每组25例。试验组分别在术中门静脉灌注及术后第3天给予颈内静脉输注脐带间充质干细胞,剂量为1×10~6/kg(制备成50 m L的细胞悬液)。两组患者均采用标准免疫抑制方案。术前,术后第3,7天,术后第1,2,3,6,12个月检测血生化、免疫功能指标,统计急、慢性排斥反应发生率,感染发生率,移植相关并发症发生率。结果与结论:(1)与对照组相比,术后第3,7天试验组外周血的CD4^+CD25^+(调节性T细胞)细胞比例高于对照组,差异有显著性意义(P<0.05),CD4^+(辅助性/诱导性T细胞)细胞比例及CD4^+/CD8^+T淋巴细胞的比值低于对照组,差异有显著性意义(P<0.05);(2)与对照组相比,试验组谷丙转氨酶、总胆红素水平差异无显著性意义(P>0.05);(3)试验组术后肝功能异常事件的发生率明显低于对照组,差异有显著性意义(P<0.05);(4)两组移植后相关并发症的发生率、感染发生率差异无显著性意义(P>0.05);(5)以上结果提示,肝移植术后静脉输注脐带间充质干细胞安全可行,早期可促进CD4^+CD25^+(调节性T细胞)的增殖和活化,降低CD4^+(辅助性/诱导性T细胞)比例及CD4+/CD8+T淋巴细胞的比值,进而改善肝移植受者免疫状态。

BACKGROUND： In recent years, the immunoregulatory effects of mesenchymal stem cells （MSCs） can be used to induce immune tolerance. OBJECTIVE： To evaluate the safety and feasibility of human umbilical cord-derived MSCs （hUC-MSCs） in liver transplantation patients. METHODS： hUC-MSCs were cultured and identified. After approved by the Medical Ethics Committee, a total of 50 patients were randomly divided into experimental group and control group according to the proportion of 1：1. In the experimental group, hUC-MSCs were perfused by the portal vein during the operation and infused into the jugular vein on the 3rd day after the operation. The injection dose was 1×106/kg （prepared as 50 mL of cell suspension）. Both groups received standard immunosuppressive regimens. Blood biochemistry and immune function indicators were detected preoperatively and at postoperative days 3, 7, months 1, 2, 3, 6, 12. Acute and chronic rejection rates, incidence of infection, and incidence of transplantation-related complications were recorded. RESULTS AND CONCLUSION： （1） At 3 and 7 days after the operation, the percentage of peripheral blood CD4＋CD25＋ cells （regulatory T cells） in the experimental group was significantly higher than that in the control group （P 0.05）. （3） The incidence of abnormal liver function in the experimental group was significantly lower than that in the control group （P 0.05）. Overall, the intravenous infusion of hUC-MSCs is safe and feasible in liver transplantation patients, which in early stage can promote the the proliferation and activation of CD4＋CD25＋ cells （regulatory T cells）, reduce the percentage of CD4＋ cells （helper/inducer T cells） and lower the ratio of CD4＋/CD8＋ T cells, thereby improving the immune status in liver transplantation patients.