脐带间充质干细胞临床前安全性考察

Pre-clinical Transplantation Safety of Human Umbilical Cord Mesenchymal Stem Cells

目的通过临床前动物实验评价,初步了解人源脐带间充质干细胞(human umbilical cord mesenchymal stem cells,h UMSCs)的生物安全性。方法选取小鼠、大鼠和裸鼠做为评价模型,使用不同剂量的h UMSCs进行评价,考察h UMSCs进入动物体内后的急性毒性反应、长期毒性反应以及致瘤性情况。结果急性毒性试验:在注射剂量不超过1.25×108个/kg时,血气学分析和剖解检测小鼠未呈现出毒性反应,h UMSCs的LD50和MTD分别为1.632×108个/kg、1.25×108个/kg。长期毒性试验:选取1.00×107个/kg、5.00×106个/kg和2.50×106个/kg三个剂量,进行12次静脉注射,观察6个月。受试大鼠注射后与对照组相比,在行为学、血气分析、血液指标检测和脏器系数比等方均未有异常变化。致瘤性试验:未有异常成瘤现象。结论本试验中,hUMSCs在受试动物体内未呈现出异常反应。

Objective Through pre-clinical animal experiment evaluation,to observe the safety of human umbilical cord mesenchymal stem cells（ hUMSCs）. Methods Using different doses of h UMSCs inject into the animals by different ways,to evaluate the acute toxicity,chronic toxicity reaction and tumorigenicity of hUMSCs. Results The acute toxicity results showed that the blood gas analysis and anatomy observation didn＇t present a toxic effects in mice when the injection dose less than 1.25×108 cells / kg,and LD50 and MTD hUMSCs respectively were 1.632×10^8 cells / kg and 1.25×108 cells / kg; Long-term toxicity test showed that different doses of h UMSCs had no abnormal change in the behavior,blood gas analysis,hematological parameters testing and the main organ coefficient. Tumorigenicity experiments showed there was no abnormal tumor formation. Conclusion In this study,we found that the hUMSCs didn＇t appear abnormal reaction in the body of animals.