骨髓间充质干细胞脱细胞神经异种移植联合G-CSF可促进坐骨神经再生。

Synapse (New York, N.y.) Pub Date : 2019-07-01 Epub Date: 2019-03-20 DOI:10.1002/syn.22093
Hua Jia, Ying Wang, Jiao Chen, Jun-Ping Li, Huai-Qin Han, Xiao-Jie Tong, Zhong-Yi He, Wen-Zhi Ma
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引用次数: 6

摘要

周围神经间隙常导致神经支配中断,表现为严重的感觉和运动功能障碍。临床上对神经损伤的修复效果不理想。骨髓基质细胞(BMSCs)负载的脱细胞神经异种移植(ANX)已被证明比脱细胞神经同种异体移植更有效。此外,粒细胞集落刺激因子(G-CSF)具有抑制炎症和细胞凋亡的作用,有利于改善轴突再生的微环境。本研究旨在探讨骨髓间充质干细胞移植ANX与G-CSF联合作用,并探讨相关机制。将成年SD大鼠随机分为5组:ANX组、ANX联合G-CSF组、bmscs转染ANX组、bmscs转染ANX联合G-CSF组、自体移植物组。移植8周后进行行为学和神经电生理检测,并对再生神经形态进行分析。进一步检测神经移植物的炎症反应和细胞凋亡,以及再生组织中生长促进因子的表达。G-CSF干预和BMSCs植入协同促进ANX桥接后周围神经再生和功能恢复,修复效果与自体神经移植相当。局部炎症减轻,骨髓间充质干细胞凋亡减少,神经调节因子水平升高。综上所述,骨髓间充质干细胞植入的ANX和G-CSF联合应用可显著改善神经化和晚期神经再生的生态位。作为自体移植的替代方案,该策略取得了良好的效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Combination of BMSCs-laden acellular nerve xenografts transplantation and G-CSF administration promotes sciatic nerve regeneration.

Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)-laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony-stimulating factor (G-CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs-seeded ANX grafting and G-CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth-promoting factors in the regenerated tissues were further assayed. G-CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs-implanted ANX and G-CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation.

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