人脐带间充质干细胞应用于肝移植患者的临床观察

发布时间：2018-06-14 18:14

本文选题：MSC + 间充质干细胞　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:长期的免疫抑制会显著提高移植受者发生恶性肿瘤和感染性疾病的概率,免疫抑制剂无法防止或者延迟慢性移植物排斥反应的发生。近年来相继有多篇文献报道间充质干细胞(MSC)具有免疫调节作用,能够诱导稳定的免疫耐受状态的产生,从而有利于降低移植免疫排斥的发生率。本实验将通过比较肝移植术后联合huc-MSC治疗患者和只接受常规免疫抑制剂治疗肝移植的患者的免疫指标、不良事件(Treatment-emergent adverse events,TEAE)发生率、相关并发症发生率、移植后肝功能的比较,来评估huc-MSC临床应用的安全性和可行性。方法:将2014年7月至2015年11月在解放军81医院肝脏移植中心实施同种异体肝移植的总计40例患者经1:1的比例按入组时间随机分入实验组和对照组,各组年龄、性别相当,随机时可按以下方式分层:移植前的ChildPugh A/B/C分级。其中实验组在肝移植术中及术后第3天给予huc-MSC静脉输注,剂量为1×106/kg(制备成50ml的细胞悬液),同时采用标准的免疫抑制方案。对照组为采用标准免疫抑制方案的肝脏移植患者。计划每位患者都将接受12个月以上的随访。评估时间点:术前;术后第3天;术后第7天;术后第1个月;术后第2个月;术后第3个月;术后第6个月;术后第12个月;各时间点评估项目有血生化;免疫功能指标;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(肝动脉并发症、门静脉并发症、胆道并发症)。一旦出现急、慢性排斥反应,患者无须等待访视时间节点,须立即到医院就诊,并退出本次研究。本实验采用SPSS 19.0统计软件完成。计量资料采用均数±标准差((?)±s)表示,两组连续变量的比较应用Wilcoxon秩和检验,计数资料用X~2检验或Fisher精确检验,P0.05认为差异有统计学意义。结果:与对照组相比,术后第3、7天实验组在外周血的CD4+CD25+(调节性T细胞)含量高于对照组,差异有统计学意义(P0.05),CD4+(辅助性/诱导性T细胞)含量及CD4+/CD8+T淋巴细胞的比值低于对照组,差异有统计学意义(P0.05),术后谷丙转氨酶、总胆红素的差异无统计学意义(P0.05),实验组术后肝功能异常事件的发生率明显低于对照组,差异有统计学意义(P0.05),两组移植后相关并发症的发生率、感染发生率的差异无统计学意义(P0.05)。结论:肝移植术后静脉输注huc-MSC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)含量及CD4+/CD8+T淋巴细胞的比值进而改善肝移植受者免疫状态。
[Abstract]:Objective: Long-term immunosuppression can significantly increase the probability of malignant tumors and infectious diseases in transplant recipients. Immunosuppressive agents can not prevent or delay the occurrence of chronic graft rejection. In recent years, it has been reported that MSCs have the ability of immune regulation, which can induce stable immune tolerance, and thus help to reduce the incidence of transplantation immune rejection. The aim of this study was to compare the immune indexes, the incidence of adverse events, the incidence of associated complications, and the liver function after liver transplantation in patients treated with huc-MSC and those who received only routine immunosuppressive therapy. To evaluate the safety and feasibility of clinical application of huc-MSC. Methods: from July 2014 to November 2015, a total of 40 patients with liver allograft were randomly divided into the experimental group and the control group according to the time of the operation. The age and sex of each group were the same as those of the control group, and 40 patients received liver allotransplantation at the liver transplantation center of the PLA 81 Hospital from July 2014 to November 2015. At random, it can be stratified as follows: Child-Pugh A / B / C grade prior to transplantation. In the experimental group, huc-MSC was given intravenously during and 3 days after liver transplantation at a dose of 1 脳 106% kg-1 脳 10 ~ (-6) 路kg ~ (-1) 50ml, and the standard immunosuppressive protocol was used. The control group was treated with standard immunosuppressive regimen for liver transplantation. Each patient is scheduled to be followed up for more than 12 months. Evaluation time points: preoperative; postoperative 3 d; postoperative 7 d; postoperative 1 month; postoperative 2 months; postoperative 3 months; postoperative 6 months; postoperative 12 months; Incidence of acute and chronic rejection; incidence of infection; incidence of transplant related complications (hepatic artery complication, portal vein complication, biliary tract complication). Once acute, chronic rejection occurs, the patient does not have to wait for the visit time node, must immediately visit the hospital, and withdraw from the study. The experiment was completed by SPSS 19.0 software. The two groups of continuous variables were compared by Wilcoxon rank sum test. The count data were calculated by X2 test or Fisher accurate test (P0.05). The difference was statistically significant. Results: compared with the control group, the CD4 CD25 (regulatory T cell) content in peripheral blood of the experimental group was higher than that of the control group on the 3rd day after operation. The difference was statistically significant (P 0.05) in CD4 (helper / inducible T cell) and the ratio of CD4 / CD8 T lymphocytes in the control group. The difference was statistically significant (P 0.05). There was no significant difference in total bilirubin (P 0.05). The incidence of abnormal hepatic function in the experimental group was significantly lower than that in the control group (P 0.05). There was no significant difference in the incidence of postoperative complications and infection between the two groups. Conclusion: intravenous infusion of huc-MSC after liver transplantation is safe and feasible, and can promote the proliferation and activation of CD4 CD25 (regulatory T cells) in the early stage. The ratio of CD4 / CD8 T lymphocytes and the ratio of CD4 / CD8 T lymphocytes were decreased to improve the immune status of the recipients of liver transplantation.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R657.3

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