脐血间充质干细胞静脉移植治疗新生大鼠缺氧缺血性脑损伤

Intravenous transplantation of umbilical blood mesenchymal stem cells after hypoxic-ischemic brain damage in neonatal rat

目的探讨脐血间充质干细胞(MSCs)静脉移植治疗新生鼠缺氧缺血性脑损伤 (HIBD)的可行性。方法将脐血MSCs移植前以DAPI标记,移植鼠在HIBD后第2周经鼠尾静脉注入脐血MSCs,于移植后第1、2和4周随机处死,行脑组织病理形态学观察,并取海马回相同部位的缺血脑组织切片,荧光镜下观察DAPI阳性细胞数。结果脐血MSCs经尾静脉移植后4周,各组鼠死亡率无显著差异,移植组脑病变率显著低于HIBD组,且该组脑组织病变仅偶见轻度,大多接近于正常,未见到重度脑组织病变发生;HIBD后1周左侧大脑缺血水肿区仍见神经细胞肿胀,细胞外间隙增宽,移植治疗1周后左侧脑组织水肿已明显减轻,上述病理组织学变化已不明显,大鼠病灶侧脑内,可见大量的DAPI阳性细胞分布,集中分布于病灶区周围,与宿主脑有机整合,没有明显的界限。结论脐血MSCs移植治疗新生鼠HIBD可以减轻脑水肿和脑损伤,在移植过程中 MSCs可以透过血脑屏障并分布在损伤的脑组织周围,未见植入反应和其他任何副作用。

Objective To study the possibility of intravenous transplantation of the human umbilical blood mesenchymal stem cells （MSCs） after hypoxic-ischemic brain damage （HIBD） in neonatal rats, Methods The umbilical blood MSCs were collected to transplant by the caudal vein of rats at the second week after HIBD , and the MSCs were marked with DAPI before implantation. The rats were divided into 3 groups ： Control group（n = 15）, HIBD group（n =20）and MSCs transplant group（n =29）. The rats in each group were randomly put to death and extracted brain tissues which were used to observe the pathomorphology,and also the hippocampal gurus was extracted to make into slices, the number of cells marked with DAPI was counted under the fluoroscope. Results The death rate of rats were no difference （P〉0, 05） in each group observed from 4 weeks after the implantation; The brain lesion rate in MSCs transplant group was significantly lower than HIBD group（P 〈 0.05） ,and the brain damage happened to most of the rats in this group was not serious and even close to the normal at the fourth week after implantation. One week after transplantation, large amount of the MSCs appeared at the damage tissue and distributed and scattered around the damage area. Conclusions Treatment of HIBD in neonate rats with HUCBMSCs implantaing can effectively decrease the brain edema and ameliorate the damaged brain tissue. During the course of trasplantation, MSCs can cross the blood brain barriert, and to distribute scattering around the damaged brain tissue. No any implantation reaction and side effect occurred.