人脐带间充质干细胞食蟹猴连续静脉输注后免疫毒性与免疫调节作用研究  

Immunotoxicity and Immunomodulatory Effects of Continuous Intravenous Infusion of Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys

作　　者：乐茜 张亚奇 周端鹏 张权 饶巍 王尉 肖翠红 石亮 韩兵 武栋成[1,2] LE Xi;ZHANG Yaqi;ZHOU Duanpeng;ZHANG Quan;RAO Wei;WANG Wei;XIAO Cuihong;SHI Liang;HAN Bing;WU Dongcheng(Wuhan University School of Basic Medical Sciences,Wuhan 430072,China;Wuhan Hamilton Biotechnology-Co.,LTD,Wuhan 430075,China)

机构地区：[1]武汉大学基础医学院,武汉430072 [2]武汉汉密顿生物科技股份有限公司,武汉430075

出　　处：《中国细胞生物学学报》2020年第4期664-672,共9页Chinese Journal of Cell Biology

基　　金：武汉市科技局前资助项目科技成果转化专项(批准号:2019030703011513);武汉市“3551光谷人才计划”资助项目(批准号:武新管人才[2019]5号)资助的课题。

摘　　要：该文旨在研究人脐带间充质干细胞在食蟹猴体内的免疫毒性与免疫调节特性。连续14天给予食蟹猴不同剂量(2.0×10^6个·kg^-1和2.0×10^7个·kg^-1)的人脐带间充质干细胞静脉滴注,检测食蟹猴血清IgG浓度、抗人脐带间充质干细胞抗体、淋巴细胞活化增殖和T细胞亚群的变化,以及胸腺和脾脏组织学变化。结果显示,连续14天静脉给予人脐带间充质干细胞对食蟹猴血清IgG浓度无影响,不刺激动物产生抗人脐带间充质干细胞抗体。人脐带间充质干细胞显著抑制食蟹猴淋巴细胞的活化增殖,降低CD3+T细胞比例,刺激Treg细胞的增殖分化。组织学检查发现,部分动物出现与给药相关的胸腺皮质萎缩和脾脏淋巴生发中心增多增大。该研究得出,人脐带间充质干细胞的免疫毒性极低,静脉输注后不引起食蟹猴体内免疫排斥等异常反应,提示其在临床上异体应用的安全性。This article studies the immunotoxicity and immunomodulatory properties of hUC-MSCs(human umbilical cord mesenchymal stem cells)in cynomolgus monkeys.The different doses of hUC-MSCs(2.0×10^6 cells·kg^-1 and 2.0×10^7cells·kg^-1)were intravenously administered to cynomolgus monkeys for 14 consecutive days.And then,serum IgG concentration was detected in cynomolgus monkeys,anti-hUC-MSCs antibodies,lymphocyte activation and proliferation,changes in T cell subsets,and histological changes in thymus and spleen.The results showed that intravenous administration of hUC-MSCs for 14 consecutive days had no effects on serum IgG concentration in cynomolgus monkeys,and did not stimulate animals to produce anti-hUC-MSCs antibodies.hUC-MSCs significantly inhibited the activation and proliferation of cynomolgus lymphocytes,decreasing the proportion of CD3+T cells,and stimulated the proliferation and differentiation of Treg cells.Histological examination revealed that some animals developed thymic cortical atrophy and increased spleen lymphagenic center associated with drug administration.The study concludes that the immunotoxicity of hUC-MSCs is extremely low.After intravenous infusion,it does not cause abnormal reactions such as immune rejection in cynomolgus monkeys,suggesting the safety of allogeneic application clinically.

关 键 词：人脐带间充质干细胞 食蟹猴 免疫原性 免疫毒性 免疫调节 

分 类 号：R392[医药卫生—免疫学]