大剂量人脐带间充质干细胞制剂给予CD-1小鼠的安全性评价

Safety evaluation of h UC-MSCs agent after large dose injection administered to CD-1 mice

目的观察单次大剂量输入自制的人脐带间充质干细胞(h UC-MSCs)制剂的急性反应,为临床研究提供安全保障。方法 60只SPF级CD-1小鼠随机分为阴性对照组、溶剂对照组和制剂组,每组雌雄各半(n=10),制剂组按1×108个细胞/kg的剂量给CD-1小鼠单次静脉注射h UC-MSCs制剂,阴性对照组和溶剂对照组分别输注同等容量的0.9%氯化钠注射液和勃脉力A溶液。输注后连续观察小鼠的临床表现、体重和摄食量。观察15 d后,将动物安乐死,进行大体解剖,观察并行组织病理学分析。结果实验期间,制剂组1只小鼠输注细胞的尾尖静脉处出现细胞堆积,引起局部毛细血管堵塞,从而导致尾尖部组织坏死。其余动物均未见异常表现和体重、食量差异,大体解剖和组织学观察未见明显与输注细胞相关的病理改变。结论 h UCMSCs制剂单次静脉注射给予CD-1小鼠无急性毒性反应。

Objective To observe the acute reaction after large dose injection of self-prepared human umbilical cord mesenchymal stem cells （hUC-MSCs） to provide safety guarantee for clinical research. Methods A total of 60 SPF-grade CD-1 mice are randomly divided into negative control group, solvent control group and preparation group. The number of each group was equally split between male and female mice （n=10）. The CD-1 mice in the preparation group were administrated with hUC-MSCs preparation by single intravenous injection according to 通讯作者：潘兴华,E-mail：xinghuapan@aliyun.com; cell/kg. The negative control group and the solvent control group were infused with 0.9% sodium chloride injection and Plasmalyte-A solution with equivalent capacity respectively. The clinical presentation, body weight and food intake of mice were continuously observed after the infusion. After 15 days of observation, euthanasia was conducted on the animals and gross anatomy was carried out for observation and histopathological analysis, Results During the experiment, one mouse in the preparation group had accumulation of infused cells in the vein at the tail tip, which caused local capillary blockage and necrosis of the tail tip. Other animals had no abnormal reaction and difference in body weight and food intake. No obvious pathological change relevant to infused cells was discovered in Gross anatomy and histological observation. Conclusion The administration of hUC-MSCs preparation to CD-1 mice by single intravenous injection causes no acute toxic reaction.