血管内皮生长因子和神经生长因子基因双重递送来增强坐骨神经再生。

Enhancement of sciatic nerve regeneration with dual delivery of vascular endothelial growth factor and nerve growth factor genes.

机构信息

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.

出版信息

J Nanobiotechnology. 2020 Mar 14;18(1):46. doi: 10.1186/s12951-020-00606-5.

DOI:10.1186/s12951-020-00606-5

PMID:32169062

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7071717/

Abstract

BACKGROUND

Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting.

RESULTS

In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study.

CONCLUSIONS

We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.

摘要

背景

周围神经损伤是一种常见的全球性临床疾病，由于其长度和较大的横截面积，坐骨神经在解剖学上是最难再生的。目前，自体神经移植仍然是治疗坐骨神经损伤最理想的策略。然而，这种方法牺牲了健康的神经，需要高度密集的手术，仍然需要其他先进的神经移植替代方法。

结果

在这项研究中，我们利用先前建立的基因传递系统，双重传递编码血管内皮生长因子(VEGF)和神经生长因子(NGF)的质粒 DNA(pDNA)，探索治疗坐骨神经损伤的方法。低分子量的支化聚乙烯亚胺(bPEI)被构建为基因载体的骨架结构，并通过醛的共轭进一步交联合成可降解的聚阳离子。在这项研究中，我们观察到 VEGF 和 NGF 蛋白在大鼠坐骨神经挤压损伤模型中的潜在协同作用。