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使用植入自体间充质干细胞的脱细胞同种异体神经移植物修复恒河猴的周围神经广泛损伤

Repair of extended peripheral nerve lesions in rhesus monkeys using acellular allogenic nerve grafts implanted with autologous mesenchymal stem cells.

作者信息

Hu Jun, Zhu Qing-Tang, Liu Xiao-Lin, Xu Yang-bin, Zhu Jia-Kai

机构信息

Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.

出版信息

Exp Neurol. 2007 Apr;204(2):658-66. doi: 10.1016/j.expneurol.2006.11.018. Epub 2007 Jan 10.

DOI:10.1016/j.expneurol.2006.11.018
PMID:17316613
Abstract

Despite intensive efforts in the field of peripheral nerve injury and regeneration, it remains difficult in humans to achieve full functional recovery following extended peripheral nerve lesions. Optimizing repair of peripheral nerve injuries has been hindered by the lack of viable and reliable biologic or artificial nerve conduits for bridging extended gaps. In this study, we utilized chemically extracted acellular allogenic nerve segments implanted with autologous non-hematopoietic mesenchymal stem cells (MSCs) to repair a 40 mm defect in the rhesus monkey ulnar nerve. We found that severely damaged ulnar nerves were structurally and functionally repaired within 6 months following placement of the MSC seeded allografts in all animals studied (6 of 6, 100%). Furthermore, recovery with the MSC seeded allografts was similar to that observed with Schwann cell seeded allografts and autologous nerve grafts. The findings presented here are the first demonstration of the successful use of autologous MSCs, expanded in culture and implanted in a biological conduit, to repair a peripheral nerve gap in primates. Given the difficulty in isolating and purifying sufficient quantities of Schwann cells for peripheral nerve regeneration, the use of MSCs to seed acellular allogenic nerve grafts may prove to be a novel and promising therapeutic approach for repairing severe peripheral nerve injuries in humans.

摘要

尽管在周围神经损伤与再生领域付出了巨大努力,但对于人类而言,在周围神经发生广泛性损伤后实现完全功能恢复仍然困难重重。由于缺乏用于桥接长间隙的可行且可靠的生物或人工神经导管,周围神经损伤修复的优化工作受到了阻碍。在本研究中,我们利用化学提取的去细胞同种异体神经段,植入自体非造血间充质干细胞(MSC),以修复恒河猴尺神经40毫米的缺损。我们发现,在所研究的所有动物(6只中的6只,100%)中,植入MSC的同种异体移植物后6个月内,严重受损的尺神经在结构和功能上均得到了修复。此外,植入MSC的同种异体移植物的恢复情况与植入雪旺细胞的同种异体移植物和自体神经移植物所观察到的情况相似。此处呈现的研究结果首次证明了在体外培养并植入生物导管中的自体MSC成功用于修复灵长类动物周围神经间隙。鉴于为周围神经再生分离和纯化足够数量雪旺细胞存在困难,利用MSC接种去细胞同种异体神经移植物可能被证明是一种用于修复人类严重周围神经损伤的新颖且有前景的治疗方法。

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