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大鼠坐骨神经缺损模型中种植骨髓间充质干细胞的去细胞神经异种移植物修复

Sciatic nerve repair by acellular nerve xenografts implanted with BMSCs in rats xenograft combined with BMSCs.

机构信息

Department of Anatomy, College of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.

出版信息

Synapse. 2012 Mar;66(3):256-69. doi: 10.1002/syn.21508. Epub 2011 Dec 13.

Abstract

Acellular nerves possess the structural and biochemical features similar to those of naive endoneurial tubes, and have been proved bioactive for allogeneil graft in nerve tissue engineering. However, the source of allogenic donators is restricted in clinical treatment. To explore sufficient substitutes for acellular nerve allografts (ANA), we investigated the effectiveness of acellular nerve xenografts (ANX) combined with bone marrow stromal cells (BMSCs) on repairing peripheral nerve injuries. The acellular nerves derived from Sprague-Dawley rats and New Zealand rabbits were prepared, respectively, and BMSCs were implanted into the nerve scaffolds and cultured in vitro. All the grafts were employed to bridge 1 cm rat sciatic nerve gaps. Fifty Wistar rats were randomly divided into five groups (n = 10 per group): ANA group, ANX group, BMSCs-laden ANA group, BMSCs-laden ANX group, and autologous nerve graft group. At 8 weeks post-transplantation, electrophysiological study was performed and the regenerated nerves were assayed morphologically. Besides, growth-promoting factors in the regenerated tissues following the BMSCs integration were detected. The results indicated that compared with the acellular nerve control groups, nerve regeneration and functional rehabilitation for the xenogenic nerve transplantation integrated with BMSCs were advanced significantly, and the rehabilitation efficacy was comparable with that of the autografting. The expression of neurotrophic factors in the regenerated nerves, together with that of brain-derived neurotrophic factor (BDNF) in the spinal cord and muscles were elevated largely. In conclusion, ANX implanted with BMSCs could replace allografts to promote nerve regeneration effectively, which offers a reliable approach for repairing peripheral nerve defects.

摘要

去细胞神经具有类似于原始神经内膜管的结构和生化特征,已被证明在神经组织工程中对同种异体移植物具有生物活性。然而,同种异体供体的来源在临床治疗中受到限制。为了探索去细胞神经同种异体移植物(ANA)的充足替代品,我们研究了去细胞神经异种移植物(ANX)与骨髓基质细胞(BMSCs)联合用于修复周围神经损伤的效果。分别从 Sprague-Dawley 大鼠和新西兰兔制备去细胞神经,并将 BMSCs 植入神经支架中进行体外培养。所有移植物均用于桥接 1cm 大鼠坐骨神经间隙。50 只 Wistar 大鼠随机分为五组(每组 n = 10):ANA 组、ANX 组、载 BMSCs 的 ANA 组、载 BMSCs 的 ANX 组和自体神经移植组。移植后 8 周,进行电生理研究,并对再生神经进行形态学检测。此外,还检测了 BMSCs 整合后再生组织中的促生长因子。结果表明,与去细胞神经对照组相比,异种神经移植与 BMSCs 整合后神经再生和功能康复明显加快,康复效果可与自体移植相媲美。再生神经中神经营养因子的表达以及脊髓和肌肉中脑源性神经营养因子(BDNF)的表达均显著升高。结论:植入 BMSCs 的 ANX 可有效替代移植物促进神经再生,为修复周围神经缺损提供了可靠的方法。

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