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雪旺细胞胶原管移植修复大鼠大段周围神经缺损。

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats.

机构信息

The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

出版信息

J Neurosurg. 2013 Sep;119(3):720-32. doi: 10.3171/2013.4.JNS121189. Epub 2013 Jun 7.

Abstract

OBJECT

Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube.

METHODS

The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only-filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel.

RESULTS

Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein-positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum-only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft.

CONCLUSIONS

The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

摘要

目的

节段性神经缺损是一个令人生畏的临床挑战,因为外周神经损伤研究已经确定,存在一个临界神经间隙长度,目前的技术无法成功桥接这个长度。用雪旺细胞(SCs)填充的神经假体可以提供一种替代治疗方法,成功修复周围神经系统中的这些长节段间隙。本研究的目的是评估自体SCs 填充在胶原管中增加节段性神经缺损可桥接长度的能力。

方法

作者研究了使用可吸收胶原管结合自体SCs(200,000 个细胞/μl)来促进坐骨神经 13mm 临界大小缺损中轴突的生长。对照组仅用血清填充逆行坐骨神经自体移植物的导管。通过在再生电缆内存在预先标记的绿色荧光蛋白阳性SCs 来评估移植SCs 的存活以及通道近端、中部和远端有髓轴突的数量。

结果

术后 4 周和 16 周,通过在再生电缆内存在预先标记的绿色荧光蛋白阳性SCs 证实了SCs 的存活。SCs 加入神经导丝显著增强了从神经残端向管内近端(p<0.001)和中点(p<0.01)再生有髓轴突的能力,在 4 周时。与仅用血清填充的导管相比,在 16 周时,整个神经导丝长度上的有髓轴突再生显著增强(p<0.001),并且与逆行自体移植物的数量相似。与逆行自体移植物相比,用胶原管修复坐骨神经的动物的自截评分明显较低,无论是无(p<0.01)还是有SCs(p<0.001)。

结论

向引导通道中添加SCs 的技术显著增强了外周神经损伤后长节段缺损的可修复间隙距离,在人类中具有应用前景。最重要的是,这项研究代表了将基于自体SCs 的治疗方法引入长节段缺损的周围神经损伤领域的一些重要的初步步骤。

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