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对侧C7转移联合接种分化脂肪干细胞的脱细胞异体神经修复大鼠臂丛上干损伤

Contralateral C7 transfer combined with acellular nerve allografts seeded with differentiated adipose stem cells for repairing upper brachial plexus injury in rats.

作者信息

Yang Jian-Tao, Fang Jin-Tao, Li Liang, Chen Gang, Qin Ben-Gang, Gu Li-Qiang

机构信息

Department of Microsurgery & Orthopedic Trauma, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.

出版信息

Neural Regen Res. 2019 Nov;14(11):1932-1940. doi: 10.4103/1673-5374.259626.

Abstract

Nerve grafting has always been necessary when the contralateral C7 nerve root is transferred to treat brachial plexus injury. Acellular nerve allograft is a promising alternative for the treatment of nerve defects, and results were improved by grafts laden with differentiated adipose stem cells. However, use of these tissue-engineered nerve grafts has not been reported for the treatment of brachial plexus injury. The aim of the present study was to evaluate the outcome of acellular nerve allografts seeded with differentiated adipose stem cells to improve nerve regeneration in a rat model in which the contralateral C7 nerve was transferred to repair an upper brachial plexus injury. Differentiated adipose stem cells were obtained from Sprague-Dawley rats and transdifferentiated into a Schwann cell-like phenotype. Acellular nerve allografts were prepared from 15-mm bilateral sections of rat sciatic nerves. Rats were randomly divided into three groups: acellular nerve allograft, acellular nerve allograft + differentiated adipose stem cells, and autograft. The upper brachial plexus injury model was established by traction applied away from the intervertebral foramen with micro-hemostat forceps. Acellular nerve allografts with or without seeded cells were used to bridge the gap between the contralateral C7 nerve root and C5-6 nerve. Histological staining, electrophysiology, and neurological function tests were used to evaluate the effect of nerve repair 16 weeks after surgery. Results showed that the onset of discernible functional recovery occurred earlier in the autograft group first, followed by the acellular nerve allograft + differentiated adipose stem cells group, and then the acellular nerve allograft group; moreover, there was a significant difference between autograft and acellular nerve allograft groups. Compared with the acellular nerve allograft group, compound muscle action potential, motor conduction velocity, positivity for neurofilament and S100, diameter of regenerating axons, myelin sheath thickness, and density of myelinated fibers were remarkably increased in autograft and acellular nerve allograft + differentiated adipose stem cells groups. These findings confirm that acellular nerve allografts seeded with differentiated adipose stem cells effectively promoted nerve repair after brachial plexus injuries, and the effect was better than that of acellular nerve repair alone. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University of China (approval No. 2016-150) in June 2016.

摘要

当采用对侧C7神经根转移术治疗臂丛神经损伤时,一直都需要进行神经移植。脱细胞异体神经移植是治疗神经缺损的一种很有前景的替代方法,并且负载分化脂肪干细胞的移植物能改善治疗效果。然而,尚未见有关这些组织工程化神经移植物用于治疗臂丛神经损伤的报道。本研究的目的是评估在大鼠模型中,负载分化脂肪干细胞的脱细胞异体神经移植物对改善神经再生的效果,该模型采用对侧C7神经转移来修复上臂丛神经损伤。从Sprague-Dawley大鼠获取分化脂肪干细胞,并将其转分化为雪旺细胞样表型。用大鼠双侧15毫米坐骨神经段制备脱细胞异体神经移植物。将大鼠随机分为三组:脱细胞异体神经移植组、脱细胞异体神经移植 + 分化脂肪干细胞组和自体移植组。通过用微型止血钳向远离椎间孔的方向牵拉来建立上臂丛神经损伤模型。用含或不含种子细胞的脱细胞异体神经移植物桥接对侧C7神经根与C5-6神经之间的间隙。术后16周,采用组织学染色、电生理学和神经功能测试来评估神经修复效果。结果显示,自体移植组可辨别的功能恢复最早开始,其次是脱细胞异体神经移植 + 分化脂肪干细胞组,然后是脱细胞异体神经移植组;此外,自体移植组与脱细胞异体神经移植组之间存在显著差异。与脱细胞异体神经移植组相比,自体移植组和脱细胞异体神经移植 + 分化脂肪干细胞组的复合肌肉动作电位、运动传导速度、神经丝和S100阳性率、再生轴突直径、髓鞘厚度以及有髓纤维密度均显著增加。这些研究结果证实,负载分化脂肪干细胞 的脱细胞异体神经移植物能有效促进臂丛神经损伤后的神经修复,且效果优于单纯脱细胞神经修复。本研究于2016年6月获得中国中山大学附属第一医院动物伦理委员会批准(批准号:2016-150)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da45/6676869/1c6e95b5a410/NRR-14-1932-g002.jpg

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