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骨髓基质细胞支持的神经外膜管修复周围神经缺损:初步报告

Peripheral nerve defect repair with epineural tubes supported with bone marrow stromal cells: a preliminary report.

作者信息

Siemionow Maria, Duggan William, Brzezicki Grzegorz, Klimczak Aleksandra, Grykien Christopher, Gatherwright James, Nair Dileep

机构信息

Department of Plastic and Reconstructive Surgery, Cleveland Clinic, Cleveland, OH, USA.

出版信息

Ann Plast Surg. 2011 Jul;67(1):73-84. doi: 10.1097/SAP.0b013e318223c2db.

DOI:10.1097/SAP.0b013e318223c2db
PMID:21629045
Abstract

INTRODUCTION

This study was performed to assess the effects of nerve gap repair with isogenic epineural tubes filled with isogenic bone marrow stromal cells (BMSC) as an alternative to autograft repair.

METHODS

A total of 24 epineural tubes were transplanted as a conduit to bridge 20 mm nerve gap defects in 2 experimental groups. In group 1, the tube was filled with saline, whereas in group 2 with isogenic BMSC prestained with PKH-dye. In all, 12 autograft sciatic nerve repairs served as a control. Sensory and motor recovery was evaluated by gastrocnemius muscle index; pinprick, toe-spread tests; and somatosensory-evoked potentials at 6 and 12 weeks postrepair. Histomorphometry and immunostaining were also performed.

RESULTS

Evidence of successful nerve regeneration was present in all animals at 6 and 12 weeks. There were no significant differences between experimental groups in functional recovery--toe-spread and pinprick tests; however, epineural conduit groups trended toward better toe-spread scores compared with autograft repair at 6 weeks. All animals had full sensory recovery as evaluated by pinprick at 12 weeks. Saline group had significantly higher gastrocnemius muscle index compared with other groups at 6 weeks; however, no differences were noted at 12 weeks. Histomorphometrical assessment did not reveal superiority of any group at 6 weeks postrepair. However, at 12 weeks, the BMSC group had significantly increased myelin thickness compared with other groups and larger diameter nerve fibers than autograft. In group 2, PKH-positive cells and expression of nerve growth factor, Laminin B2, glial fibrillary acidic protein, and vascular endothelial growth factor were confirmed. nerve growth factor- and glial fibrillary acidic protein-positive BMSC were also found inside the tube.

CONCLUSION

The epineural tube is a viable, naturally occurring biologic conduit for nerve repair. Cotransplantation of BMSC-enhanced nerve regeneration by means of increased myelinization and expression of neurotrophic factors. Overall, obtained results with epineural tube/BMSC construct were comparable to autograft repair.

摘要

引言

本研究旨在评估用填充同基因骨髓基质细胞(BMSC)的同基因神经外膜管修复神经缺损作为自体移植修复替代方法的效果。

方法

在2个实验组中,共移植24个神经外膜管作为导管来桥接20mm的神经缺损。在第1组中,管内填充生理盐水,而在第2组中填充用PKH染料预染色的同基因BMSC。总共12例自体坐骨神经修复作为对照。在修复后6周和12周,通过腓肠肌指数、针刺、足趾展开试验以及体感诱发电位评估感觉和运动恢复情况。还进行了组织形态计量学和免疫染色。

结果

在6周和12周时,所有动物均有神经成功再生的证据。实验组在功能恢复方面(足趾展开和针刺试验)无显著差异;然而,在6周时,神经外膜导管组的足趾展开评分相比自体移植修复有更好的趋势。在12周时,通过针刺评估所有动物均有完全的感觉恢复。在6周时,生理盐水组的腓肠肌指数显著高于其他组;然而,在12周时未观察到差异。组织形态计量学评估在修复后6周未显示任何一组具有优越性。然而,在12周时,BMSC组与其他组相比髓鞘厚度显著增加,且神经纤维直径比自体移植组大。在第2组中,证实了PKH阳性细胞以及神经生长因子、层粘连蛋白B2、胶质纤维酸性蛋白和血管内皮生长因子的表达。在管内还发现了神经生长因子和胶质纤维酸性蛋白阳性的BMSC。

结论

神经外膜管是一种可行的、天然存在的用于神经修复的生物导管。BMSC的共移植通过增加髓鞘形成和神经营养因子的表达促进了神经再生。总体而言,神经外膜管/BMSC构建体获得的结果与自体移植修复相当。

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