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骨髓基质细胞与雪旺细胞共移植到去细胞神经支架中用于大鼠坐骨神经再生

Co-Graft of Bone Marrow Stromal Cells and Schwann Cells Into Acellular Nerve Scaffold for Sciatic Nerve Regeneration in Rats.

作者信息

Zhou Li-Na, Zhang Ji-Wei, Liu Xiao-Lin, Zhou Li-Hua

机构信息

Lectorate, Department of Anatomy, Guangdong Medical College, Zhanjiang, China.

Resident-in-Training, Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

J Oral Maxillofac Surg. 2015 Aug;73(8):1651-60. doi: 10.1016/j.joms.2015.02.013. Epub 2015 Mar 16.

DOI:10.1016/j.joms.2015.02.013
PMID:25959876
Abstract

PURPOSE

The conventional strategy for bridging large nerve defects, namely nerve autograft transplantation, results in donor-site morbidity. This detrimental consequence currently drives the search for alternatives. The authors used an acellular nerve scaffold filled with bone marrow stromal cells (BMSCs) and Schwann cells (SCs) to enhance regeneration.

MATERIALS AND METHODS

In 60 adult rats, a 10-mm sciatic nerve defect was bridged with a nerve autograft (positive control), an acellular nerve scaffold (negative control), an acellular nerve scaffold with BMSCs (group I), an acellular nerve scaffold with SCs (group II), or an acellular nerve scaffold with BMSCs plus SCs (group III). After regenerating for 4 and 16 weeks after surgery, nerve regeneration was functionally assessed by a walking track analysis. The compound muscle action potential (CMAP), nerve conduction velocity (NCV) along regenerated sciatic nerves, and gastrocnemius muscle index (GMI) were recorded to assess the conduction properties and extent of denervation atrophy. The number of retrograde-labeled lumbar motor neurons identified by fluorescent dyes in the ipsilateral ventral horn and spinal ganglia were counted to assess the regeneration of axons.

RESULTS

After 4 and 16 weeks, improvement of the sciatic function index of the sciatic nerve in group III was statistically greater than that of the negative control group, group I, and group II. At 16 weeks after grafting, obvious differences in the GMI were found among groups. Group III had a statistical increase in GMI compared with the negative control group, group I, and group II. The CMAP and NCV measurements showed comparable results at 16 weeks after reconstruction: group III had statistically better results compared with the negative control group, group I, and group II. Fluorescent dye analysis of the retrograde-labeled lumbar motoneurons in the ipsilateral ventral horn and spinal ganglia showed that more motor neurons in the ipsilateral ventral horns and spinal ganglia were labeled in group III than in the negative control group, group I, and group II at 16 weeks after the operation. All results consistently showed that when BMSCs and SCs were loaded together in an acellular nerve scaffold, functional recovery of the sciatic nerve was enhanced to the greatest degree among the 3 cell-treated groups; furthermore, its beneficial effect on sciatic injury regeneration was similar to the autograft group, although it never exceeded it.

CONCLUSIONS

This study is a step forward in the search for an alternative to the nerve autograft because it showed that co-grafting of BMSCs and SCs into an acellular nerve scaffold enhanced sciatic nerve functional recovery in rats. Its beneficial effect on sciatic injury regeneration was similar to the autograft group, although it did not exceed it.

摘要

目的

用于桥接大神经缺损的传统策略,即神经自体移植,会导致供体部位出现并发症。这种有害后果目前促使人们寻找替代方法。作者使用填充有骨髓基质细胞(BMSCs)和雪旺细胞(SCs)的脱细胞神经支架来促进神经再生。

材料与方法

在60只成年大鼠中,用神经自体移植(阳性对照)、脱细胞神经支架(阴性对照)、含BMSCs的脱细胞神经支架(I组)、含SCs的脱细胞神经支架(II组)或含BMSCs加SCs的脱细胞神经支架(III组)桥接10毫米的坐骨神经缺损。术后再生4周和16周后,通过行走轨迹分析对神经再生进行功能评估。记录复合肌肉动作电位(CMAP)、沿再生坐骨神经的神经传导速度(NCV)和腓肠肌指数(GMI),以评估神经传导特性和失神经萎缩程度。对同侧腹角和脊髓神经节中通过荧光染料鉴定的逆行标记腰运动神经元数量进行计数,以评估轴突再生情况。

结果

4周和16周后,III组坐骨神经的坐骨神经功能指数改善在统计学上显著大于阴性对照组、I组和II组。移植后16周,各组间GMI存在明显差异。与阴性对照组、I组和II组相比,III组GMI有统计学意义的增加。重建后16周时CMAP和NCV测量结果显示类似情况:与阴性对照组、I组和II组相比,III组在统计学上结果更好。对同侧腹角和脊髓神经节中逆行标记腰运动神经元的荧光染料分析表明,术后16周时,III组同侧腹角和脊髓神经节中标记的运动神经元比阴性对照组、I组和II组更多。所有结果一致表明,当BMSCs和SCs一起加载到脱细胞神经支架中时,在3个细胞处理组中坐骨神经的功能恢复得到最大程度增强;此外,其对坐骨神经损伤再生的有益作用与自体移植组相似,尽管从未超过自体移植组。

结论

这项研究在寻找神经自体移植替代方法方面向前迈进了一步,因为它表明将BMSCs和SCs共同移植到脱细胞神经支架中可增强大鼠坐骨神经的功能恢复。其对坐骨神经损伤再生的有益作用与自体移植组相似,尽管未超过自体移植组。

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