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联合沃顿胶源性间充质干细胞与神经导管:一种治疗周围神经损伤的潜在有效疗法。

Combined Wharton's jelly derived mesenchymal stem cells and nerve guidance conduit: A potential promising therapy for peripheral nerve injuries.

作者信息

Shalaby Sally M, El-Shal Amal S, Ahmed Faiza E, Shaban Sahar F, Wahdan Rania A, Kandel Wael A, Senger Mohammed S

机构信息

Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

Int J Biochem Cell Biol. 2017 May;86:67-76. doi: 10.1016/j.biocel.2017.03.002. Epub 2017 Mar 6.

DOI:10.1016/j.biocel.2017.03.002
PMID:28274689
Abstract

BACKGROUND

Peripheral nerve injuries represent a clinical problem with insufficient or unsatisfactory treatment options. Functional outcome with nerve guidance conduits was unsatisfactory in nerve defects with increased gap size. So, cell therapy may benefit as a tool for optimizing the regeneration process. The aim of the present study was to evaluate the impact of combination of cell therapy and nerve guidance conduits on the nerve regeneration and on the expression of the factors aiding the regeneration in a rat model of sciatic nerve injury.

METHODS AND RESULTS

Sixty Wistar rats were randomly divided into four groups: Group I: normal control group; Group II: sciatic nerve injury (SNI) with a 10mm long sciatic nerve gap; Group III: SNI with using a nerve conduit (NC) for nerve gap bridging; and Group IV: SNI with using a NC associated with Wharton's jelly derived mesenchymal stem cells (WJ-MSCs). The results showed that the combination therapy NC+WJ-MSCs caused much better beneficial effects than NC alone evidenced by increasing sciatic nerve index and pin-prick score. The histopathological analysis found that the use of the NC combined with WJ[HYPHEN]MSCs resulted in a structure of the sciatic nerve comparable to the normal one with better nerve regeneration when compared with NC only. There was no differentiation of WJ-MSCs into nerve structure. Lastly, there was an upregulation of expression for netrin-1, ninjurin, BDNF, GDNF, VEGF and angiopoitin-1 rat genes in NC+WJ-MSCs group than NC alone.

CONCLUSION

The addition of WJ-MSCs to the nerve guidance conduits seems to bring significant advantage for nerve regeneration, basically by increasing the expression of neurotrophic and angiogenic factors establishing more favorable environment for nerve regeneration.

摘要

背景

周围神经损伤是一个临床问题,其治疗选择不足或不尽人意。在神经缺损间隙增大的情况下,神经引导导管的功能结果并不理想。因此,细胞治疗作为优化再生过程的一种工具可能会有所帮助。本研究的目的是评估细胞治疗与神经引导导管相结合对坐骨神经损伤大鼠模型中神经再生以及对促进再生的因子表达的影响。

方法与结果

60只Wistar大鼠随机分为四组:第一组:正常对照组;第二组:坐骨神经损伤(SNI),坐骨神经间隙长10mm;第三组:SNI,使用神经导管(NC)桥接神经间隙;第四组:SNI,使用与沃顿胶衍生间充质干细胞(WJ-MSCs)相关的NC。结果表明,联合治疗NC+WJ-MSCs比单独使用NC产生了更好的有益效果,坐骨神经指数和针刺评分增加证明了这一点。组织病理学分析发现,与仅使用NC相比,使用NC联合WJ-MSCs导致坐骨神经结构与正常结构相当,神经再生更好。WJ-MSCs没有分化为神经结构。最后,与单独使用NC相比,NC+WJ-MSCs组中netrin-1、ninjurin、BDNF、GDNF、VEGF和血管生成素-1大鼠基因的表达上调。

结论

在神经引导导管中添加WJ-MSCs似乎为神经再生带来了显著优势,主要是通过增加神经营养和血管生成因子的表达,为神经再生建立更有利的环境。

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