Liu Xiao xuan, Fan Dong sheng, Zhang Jun, Zheng Ju yang, Ma Tie min
Department of neurology, Peking University Third Hospital, Beijing 100083, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2008 Apr;40(2):185-91.
To explore the better transplantation way of mesenchymal stem cells (MSCs) in neuromuscular disease and its effect on the recovery of injured sciatic nerves.
Human MSCs were isolated, cultured and fluorescently labeled in vitro. Fifty-four rats were randomly divided into MSC intramuscular (ims), intravenous (iv) and saline administration groups. The sciatic nerve was crashed by hemostat for 5 min. MSCs (10(6)) were injected 3 days after injury. Sciatic nerve function index (SFI), electromyography and muscle biopsy specimens were recorded on ad3, ad7,ad14, ad21, ad28 and ad60.
Denervation and regeneration of nerves were observed in the three groups. Spontaneous activity and action potential happened earlier in ims injected group than in the other two groups. The nerve conductivity velocity of ims injected rats was significantly faster than those of the iv group and the control group on d14 [(32.27+/-7.42) m/s,(22.92+/-7.34) m/s and (17.67+/-5.52) m/s; F=5.661,P=0.042]. On d60, the conduction velocity was about the same among the three groups(P>0.05). However, compound muscle action potential (CMAP) amplitude in ims injected group was significantly higher as compared with the other two groups[ims injected group (12.50+/-2.06) mV, iv group (1.50+/-0.20) mV, control group (10.13+/-4.04) mV, F=6.347, P=0.033]. The MSCs were able to be observed only in ims injected tissues 3 weeks after implantation (A large number of small undifferentiated cells were found outside the myofibers and some were found between the cells.) The atrophy of gastrocnemius in ims injected group was much less severe than that of the other 2 groups. The diameter of muscle fibers was significantly longer on d60 (F=4.537, P=0.021).
Intramuscular injection of MSC was well distributed in denervated muscle, which provides a new way of nerve regeneration in the rat model of sciatic nerve injury.
探讨间充质干细胞(MSCs)在神经肌肉疾病中更好的移植方式及其对损伤坐骨神经恢复的影响。
体外分离、培养和荧光标记人MSCs。54只大鼠随机分为MSCs肌肉注射组、静脉注射组和生理盐水注射组。用止血钳夹闭坐骨神经5分钟。损伤后3天注射10⁶个MSCs。分别在术后3天、7天、14天、21天、28天和60天记录坐骨神经功能指数(SFI)、肌电图和肌肉活检标本。
三组均观察到神经失神经支配和再生。肌肉注射组的自发活动和动作电位出现时间早于其他两组。术后14天,肌肉注射组大鼠的神经传导速度明显快于静脉注射组和对照组[(32.27±7.42)m/s、(22.92±7.34)m/s和(17.67±5.52)m/s;F=5.661,P=0.042]。术后60天,三组的传导速度大致相同(P>0.05)。然而,肌肉注射组的复合肌肉动作电位(CMAP)幅度明显高于其他两组[肌肉注射组(12.50±2.06)mV,静脉注射组(1.50±0.20)mV,对照组(10.13±4.04)mV,F=6.347,P=0.033]。移植3周后,仅在肌肉注射组的组织中观察到MSCs(在肌纤维外发现大量未分化的小细胞,部分细胞间也有发现)。肌肉注射组腓肠肌的萎缩程度明显轻于其他两组。术后60天,肌纤维直径明显更长(F=4.537,P=0.021)。
肌肉注射MSCs在失神经支配的肌肉中分布良好,为大鼠坐骨神经损伤模型的神经再生提供了一种新途径。