Schwann Cells Transduced with a Lentiviral Vector Encoding Fgf-2 Promote Motor Neuron Regeneration Following Sciatic Nerve Injury
Schwann Cells Transduced with a Lentiviral Vector Encoding Fgf-2 Promote Motor Neuron Regeneration Following Sciatic Nerve Injury
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DOI：
10.1002/glia.22712
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发表时间：
2014-10-01
期刊：
影响因子：
6.2
通讯作者：
Udina, Esther
中科院分区：
文献类型：
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作者：
Allodi, Ilary;Mecollari, Vasil;Udina, Esther
成纤维细胞生长因子2 （FGF-2）是一种由神经胶质细胞和不同神经元群体表达的营养因子。在脊髓和背根神经节（DRG）外植体中添加FGF-2表明，FGF-2特异性地促进了运动神经元轴突的生长。为了进一步探索FGF-2促进轴突再生的潜在能力，我们制作了一个慢病毒载体（LV）在损伤大鼠周围神经中过表达FGF-2 （LV- fgf2）。用FGF-2转导培养的雪旺细胞，加入胶原基质包埋脊髓或DRG外植体中，可显著增加运动神经突的生长，但不增加感觉神经突的生长。LV-FGF2在体外促进运动轴突生长的效果与直接添加营养因子相同。将LV-FGF2直接注射到大鼠坐骨神经后，FGF-2的表达增加，FGF-2位于雪旺细胞基底层。为了研究FGF-2过表达对神经损伤后轴突再生的体内影响，我们将LV-FGF2转导的雪旺细胞移植到硅胶管中，用于修复切除的大鼠坐骨神经。损伤后2个月进行的电生理测试显示，LV-FGF2治疗的动物后肢肌肉神经再生加速且更加明显，随访结束时到达胫骨远端神经的运动和感觉神经元数量增加。
Fibroblast growth factor 2 (FGF-2) is a trophic factor expressed by glial cells and different neuronal populations. Addition of FGF-2 to spinal cord and dorsal root ganglia (DRG) explants demonstrated that FGF-2 specifically increases motor neuron axonal growth. To further explore the potential capability of FGF-2 to promote axon regeneration, we produced a lentiviral vector (LV) to overexpress FGF-2 (LV-FGF2) in the injured rat peripheral nerve. Cultured Schwann cells transduced with FGF-2 and added to collagen matrix embedding spinal cord or DRG explants significantly increased motor but not sensory neurite outgrowth. LV-FGF2 was as effective as direct addition of the trophic factor to promote motor axon growth in vitro. Direct injection of LV-FGF2 into the rat sciatic nerve resulted in increased expression of FGF-2, which was localized in the basal lamina of Schwann cells. To investigate the in vivo effect of FGF-2 overexpression on axonal regeneration after nerve injury, Schwann cells transduced with LV-FGF2 were grafted in a silicone tube used to repair the resected rat sciatic nerve. Electrophysiological tests conducted for up to 2 months after injury revealed accelerated and more marked reinnervation of hindlimb muscles in the animals treated with LV-FGF2, with an increase in the number of motor and sensory neurons that reached the distal tibial nerve at the end of follow-up.