大鼠肌肉注射移植人脐带间充质干细胞的安全性

Safety of human umbilical cord mesenchymal stem cells transplanted into rats by intramuscular injection

背景:目前国内关于间充质干细胞肌肉注射安全性方面的研究报道较少。目的:观察人脐带间充质干细胞肌肉注射后,移植大鼠各项生理指标及注射局部肌肉组织的病理学变化。方法:SPF级雄性Wistar大鼠51只,取3只作为空白对照,剩余48只随机均分为4组:低、中、高浓度细胞移植组分别于大鼠左下肢腓肠肌外侧肌肉注射2.5×109L-1,5×109L-1,1.5×1010L-1人脐带间充质干细胞悬液,共注射2个位点,每个位点注射0.1mL,2个位点间隔约0.5cm;溶媒对照组同法注射50g/L葡萄糖溶液。分别于注射后1d及1,2,4周进行大鼠尿常规、血液学、血液生化学和病理组织学检查。结果与结论:人脐带间充质干细胞肌肉注射后对大鼠尿常规及肝脏、肾脏均无明显影响;仅引起总胆红素一过性升高,以及血小板、乳酸脱氢酶和肌酸激酶同工酶轻度炎症反应性升高;高浓度细胞移植可引起肌肉注射局部明显炎症反应。提示人脐带间充质干细胞免疫原性极低,在掌握了细胞移植的适宜浓度及剂量的前提下,以肌肉注射的方式进行异种移植不会引起受者严重的免疫排斥反应。

BACKGROUND：A few reports have addressed the safety of mesenchymal stem cells（MSCs） by intramuscular injection in China.OBJECTIVE：To observe each physiological index and pathological changes of local muscle tissue following human umbilical cord MSCs（HUMSCs） transplanted into rat muscle by intramuscular injection.METHODS：In a total of 51 male SPF Wistar rats,three served as blank controls,and the remaining was randomly divided into four groups.2.5×109/L,5×109/L,1.5×1010/L HUMSCs were respectively injected into the gastrocnemius of the left lower limb of rats of low,moderate and high cell concentration groups,totally two entry sites,0.1 mL/site.The distance between two sites was 0.5 cm.50 g/L glucose solution was infused into rats of the solvent control group.Urine routine test,blood routine test,hematological and biochemical test and histopathologic examination were conducted at 1 day,1,2,4 weeks following injection.RESULTS AND CONCLUSION：No significant effect was observed on urine routine test and histopathologic examination of liver and kidney after injection of HUMSCs.Total bilirubin levels were transient,or platelet,lactate dehydrogenase,and creatine kinase-MB levels slightly higher exceeding upper normal range caused by inflammatory reaction.High cell concentration could cause significant inflammatory reaction in the injection site of muscle tissues.Results have suggested that HUMSCs do not induce severe immunoreactivity even to xenografts by intramuscular injection owing to their low immunogenicity under suitable concentration and dose of cell transplantation.