Mesenchymal Stem Cells in a Polycaprolactone Conduit Promote Sciatic Nerve Regeneration and Sensory Neuron Survival after Nerve Injury
Mesenchymal Stem Cells in a Polycaprolactone Conduit Promote Sciatic Nerve Regeneration and Sensory Neuron Survival after Nerve Injury
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DOI：
10.1089/ten.tea.2011.0496
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发表时间：
2012-10-01
影响因子：
4.1
通讯作者：
Blanco Martinez, Ana Maria
中科院分区：
文献类型：
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作者：
Frattini, Flavia;Pereira Lopes, Fatima Rosalina;Blanco Martinez, Ana Maria
尽管外周神经系统在创伤性损伤后能够再生，但损伤后的功能结果是有限和差的。骨髓间充质干细胞（MSCs）是一种多能细胞，已被用于周围神经再生的研究，并取得了可喜的成果。本研究的目的是评估神经横断后，MSC治疗到聚己内酯（PCL）神经导向器中的小鼠坐骨神经再生和神经元存活。将C57 BL/6小鼠的左侧坐骨神经横切，并将神经残端置于生物可降解的PCL管中，在它们之间留下3 mm的间隙;该管用从GFP+动物获得的MSC（MSC处理组）或用培养基（Dulbecco改良的Eagle培养基组）填充。根据坐骨神经功能指数（SFI）分析运动功能。6周后，将动物安乐死，收集再生的坐骨神经、背根神经节（DRG）、脊髓和腓肠肌并进行光镜和电镜处理。再生神经的定量分析显示，在神经导管内接受干细胞的组中，有髓纤维的数量显著增加。MSC治疗组DRG中的神经元数量显著增加，而脊髓中的运动神经元数量无差异。我们还发现MSC治疗组中营养因子表达值更高，尤其是神经生长因子。SFI显示MSC治疗组有显著改善。腓肠肌的重量和肌酸磷酸激酶水平增加，表明接受MSC的动物的神经再支配和活动得到改善。免疫组织化学证明，一些GFP+移植的细胞假定Schwarm细胞样表型，证明了他们的S-100蛋白，雪旺细胞标志物的表达。我们的研究结果表明，使用充满MSC的PCL管是一种很好的策略，以改善神经横断后的小鼠神经再生。
Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwarm-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell marker. Our findings suggest that using a PCL tube filled with MSCs is a good strategy to improve nerve regeneration after a nerve transection in mice.