School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, China.
Tissue Eng Regen Med. 2023 Apr;20(2):309-322. doi: 10.1007/s13770-022-00517-6. Epub 2023 Mar 6.
Repair of long-distance peripheral nerve defects remains an important clinical problem. Nerve grafts incorporated with extracellular vesicles (EVs) from various cell types have been developed to bridge peripheral nerve defects. In our previous research, EVs obtained from skin-derived precursor Schwann cells (SKP-SC-EVs) were demonstrated to promote neurite outgrowth in cultured cells and facilitate nerve regeneration in animal studies.
To further assess the functions of SKP-SC-EVs in nerve repair, we incorporated SKP-SC-EVs and Matrigel into chitosan nerve conduits (EV-NG) for repairing a 15-mm long-distance sciatic nerve defect in a rat model. Behavioral analysis, electrophysiological recording, histological investigation, molecular analysis, and morphometric assessment were carried out.
The results revealed EV-NG significantly improved motor and sensory function recovery compared with nerve conduits (NG) without EVs incorporation. The outgrowth and myelination of regenerated axons were improved, while the atrophy of target muscles induced by denervation was alleviated after EVs addition.
Our data indicated SKP-SC-EVs incorporation into nerve grafts represents a promising method for extended peripheral nerve damage repair.
修复长距离周围神经缺损仍然是一个重要的临床问题。已经开发出了各种细胞类型的细胞外囊泡(EVs)与神经移植物结合,以桥接周围神经缺损。在我们之前的研究中,已经证明来源于皮肤衍生前体细胞 Schwann 细胞(SKP-SC-EVs)的 EVs 可促进培养细胞中的突起生长,并促进动物研究中的神经再生。
为了进一步评估 SKP-SC-EVs 在神经修复中的功能,我们将 SKP-SC-EVs 和 Matrigel 纳入壳聚糖神经导管(EV-NG)中,以修复大鼠模型中的 15mm 长距离坐骨神经缺损。进行了行为分析、电生理记录、组织学研究、分子分析和形态计量评估。
结果表明,与未加入 EVs 的神经导管(NG)相比,EV-NG 显著改善了运动和感觉功能的恢复。加入 EVs 后,再生轴突的生长和髓鞘形成得到改善,同时减轻了去神经支配引起的靶肌肉萎缩。
我们的数据表明,将 SKP-SC-EVs 纳入神经移植物是修复长距离周围神经损伤的一种很有前途的方法。