人脐带间充质干细胞多次输注食蟹猴安全性研究  

A safety study of multiple-administration human umbilical cord mesenchymal stem cells in cynomolgus monkeys

作　　者：朱灏 郝晓芳 黄瑛 Zhu Hao;Hao Xiao-fang;Huang Ying(Sinoneural Cell Engineering Group Co.,Ltd.,Shanghai 200240,China;National Drug Safety Evaluation and Monitoring Center of China Food and Drug Identification and Research Institute,Beijing Key Laboratory of Drug Non Clinical Safety Evaluation,Beijing 100176,China)

机构地区：[1]华夏源细胞工程集团股份有限公司,上海200240 [2]中国食品药品鉴定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室,北京100176

出　　处：《兰州大学学报（医学版）》2022年第2期21-25,共5页Journal of Lanzhou University（Medical Sciences）

基　　金：闵行区2019年度重大产业技术攻关计划项目(2019MH-ZD01);中国科学院战略性先导科技专项(XDA16040502);国家重点研究发展计划课题资助项目(2016YFA0101503)。

摘　　要：目的评估人脐带间充质干细胞(hUC-MSCs)多次输注食蟹猴的安全性,为hUC-MSCs临床应用的安全性提供支持。方法取第5代(P5)hUC-MSCs进行形态学、三向分化及免疫表型鉴定后静脉输注食蟹猴,分为低剂量组和高剂量组,每组3只,共输注5次,1次/周。在规定的时间点测量体温、体重、血压、血常规、血生化、血清IgG/IgM以及血液CD4^(+)/CD8^(+)T细胞,评估hUC-MSCs多次静脉输注后对食蟹猴的急性和长期毒性。结果获取的P5代hUC-MSCs符合典型的间充质干细胞特征。食蟹猴在接受3.0×10^(6) cells/kg或2.0×10^(7) cells/kghUC-MSCs多次静脉输注后不同的时间点检测,生理生化指标与输注前相比差异无统计学意义(P>0.05)。结论P5代hUC-MSCs在3.0×10^(6) cells/kg或2.0×10^(7) cells/kg剂量下多次静脉输注食蟹猴是安全的。Objective To evaluate the safety of multiple administrations of human umbilical cord mesenchy-mal stem cells(hUC-MSCs)in cynomolgus monkeys,hoping to provide safety hints for the clinical applica-tion of hUC-MSCs.Methods hUC-MSCs at passage 5(P5)were characterized by morphology,surface marker prolife and trilineage differential potential.Then P5 hUC-MSCs were intravenously infused into cyno-molgus monkeys for 5 times(once per week).Six cynomolgus monkeys were randomly divided into low-dose(3.0×10^(6) cells/kg,3 animals)or high-dose(2.0×10^(7) cells/kg,3 animals)treatment groups.To evaluate the acute and long-term toxicity exerted by hUC-MSCs infusion,body temperature,body weight,blood pressure,blood routine test,blood biochemistry,serum IgG/IgM level,and the ratio of CD4+and CD8+T cells were determined at different time points.Results P5 hUC-MSCs were verified to exhibit typical MSC character-istics.The physiological and biochemical values of cynomolgus monkeys receiving multiple intravenous infusions of hUC-MSCs(3.0×10^(6) cells/kg or 2.0×10^(7) cells/kg)at different time points were not significantly different from those before infusion(P>0.05).Conclusion It is safe for cynomolgus monkeys to undergo multiple intravenous injections of P5 hUC-MSCs at a dosage of 3.0×10^(6) cells/kg or 2.0×10^(7) cells/kg.

关 键 词：人脐带间充质干细胞 食蟹猴 安全性 

分 类 号：R99[医药卫生—毒理学]