APPLICATION OF FETAL NEURAL STEM CELLS TRANSPLANTATION IN DELAYING DENERVATED MUSCLE ATROPHY IN RATS WITH PERIPHERAL NERVE INJURY
APPLICATION OF FETAL NEURAL STEM CELLS TRANSPLANTATION IN DELAYING DENERVATED MUSCLE ATROPHY IN RATS WITH PERIPHERAL NERVE INJURY
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胎儿神经干细胞移植在延缓周围神经损伤大鼠失神经性肌萎缩中的应用
DOI：
10.1002/micr.20722
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发表时间：
2010-01-01
期刊：
影响因子：
2.1
通讯作者：
Xu, Jianguang
中科院分区：
文献类型：
--
作者：
Gu, Shihui;Shen, Yundong;Xu, Jianguang
周围神经损伤常导致进行性骨骼肌萎缩和功能恢复不良。以往的研究表明，将神经干细胞移植到周围神经中可以分化为神经元，延缓肌肉萎缩。然而，其机制并不十分清楚。在这项研究中，我们将胚胎神经干细胞移植到损伤的神经，并检查新形成的神经肌肉接头（NMJs）在失神经支配的肌肉和肌肉萎缩的逮捕。本研究选用2只妊娠Fischer大鼠作为胚胎神经干细胞的获取对象，70只大鼠随机分为神经干细胞移植组和对照组，5只未手术大鼠作为正常对照。两组均于胫神经切断后将5 μ l含或不含胚胎神经干细胞的培养液（5 × 10 6）分别移植于胫神经远端残端。与对照组相比，神经干细胞移植组在失神经后3、5、7个月时腓肠肌干重显著增加，肌纤维面积显著保留（P < 0.05）。胚胎神经干细胞移植后7个月，胫神经远端仍有神经元生长。免疫组化检测新生NMJ。此外，电生理分析和逆行追踪结果表明，肌肉与分化神经元之间的神经通路是完整的。结论：胚胎神经干细胞移植到周围神经内可分化为神经元，并与失神经肌肉形成功能性NMJ，这可能有利于周围神经损伤后肌肉萎缩的治疗。(c)2009威利-利斯公司显微外科30：266-274，2010。
Injury to peripheral nerves always results in progressive skeletal muscle atrophy and poor functional recovery. Previous studies have demonstrated that transplanting neural stem cells (NSCs) into peripheral nerve can differentiate into neurons and delay muscle atrophy. However, the mechanism was not very clear. In this study, we transplanted the fetal NSCs to the injured nerve and examined new formed neuromuscular junctions (NMJs) in the denervated muscle and arrest of muscle atrophy. In our study, two pregnant Fischer rats were used to harvest fetal NSCs, 70 rats were randomly divided into NSC-transplanted and control groups, five rats without surgery were used as the normal control. A volume of 5 mu l culture media with or without fetal NSCs (5 x 10(6)) were transplanted into distal tibial nerve stump after the nerve was transected in two groups, respectively. Three, five, and seven months after denervation, the dry weight of gastrocnemius muscle was found significant heavier, and the fiber area was more retained in NSC-transplanted group comparing to the control group (P < 0.05). Neurons were found in the distal tibial nerves even 7 months after fetal NSCs transplantation. Newly formed NMJs were detected by immunohistochemistry. In addition, the results of electrophysiological analysis and retrograde tracing manifested that the neural pathway between muscle and differentiated neurons was integrity. In conclusions, our study demonstrated that fetal NSCs transplanted into peripheral nerves could differentiate into neurons and form functional NMJs with denervated muscle, which may be beneficial for the treatment of muscle atrophy after peripheral nerve injury. (c) 2009 Wiley-Liss, Inc. Microsurgery 30:266-274, 2010.