人脐带间充质干细胞静脉输注小鼠的安全性

A safety study of intravenous injection of human umbilical cord mesenchymal stem cells in mice

目的探讨C57/BL6J小鼠重复多次尾静脉输注人脐带间充质干细胞后的免疫反应和毒性。方法将SPF级别的32只C57/BL6J小鼠随机分为阴性对照组、细胞移植组,每组16只,雌雄各半,细胞移植组小鼠尾静脉注射分离培养的第5代人脐带间充质干细胞,一次5×106/只,每周注射一次,连续注射4周;阴性对照组每次注射相同容积的PBS。注射后后观察小鼠的一般症状,末次注射后1周、4周进行血细胞计数、血生化、免疫反应指标、脏器质量测定和组织病理学检查。结果细胞移植组小鼠血细胞计数、血生化、脏器重量和脏器系数与对照组无显著性差异(P>0.05),脏器组织病理学在光镜下检查结果与对照组无形态学差别,以及免疫结果测定(T细胞亚群CD3+、CD4+、CD8+及CD4+/CD8+)与对照组无显著性差异(P>0.05)。结论人脐带间充质干细胞重复多次尾静脉输注C57/BL6J小鼠是安全可行的,对受者无明显免疫反应和毒副作用。

Objective To study the toxicity of intravenous injection of human umbilical cord mesenchymal stem cells in C57/BL6J mice with repeated administrations. Methods 32 SPF C57/BL6J mice were randomly divided into negative control group and HUMSC transplantation group, of equal gender. HUMSCs were isolated and subsequently cultured through 5 passages in vitro. 5 x 106 HUMSCs were injected each mice of transplantation group via tail vein once 1 week for 4 weeks, and the equal quantity PBS were injected to control group mice. Mice were euthanatized on the day of 1 week （8 mice per group） and 4 weeks （all survived mice） after the last treatment following the schedule. Toxicity was evaluated by clinical observations, pathology （blood cell counts, clinical biochemistry）, immunologic consequences,visceral organs weight and anatomic pathology. Results No significant difference in hematological and biochemical parameters between HUMSC transplantation group and control group （P 〉 0. 05）. There was also no significant change in organ weight or organ coefficient between the two groups（P 〉 0.05 ）. There was no significant change in the subpopulation of T-cells （the percentage of CD3, CD4, CD8 T cells, and the ratio of CD4 and CD8 T cells）. HUMSC transplantation group did not show any histopathological change in the viscera organs compared to control group. Conclusion Results have suggested that intravenous injection of HUMSCs in C57/BL6J mice with repeated administrations is safe and feasible. No side effects and immune response were found in recipients.