Hu Taotao, Chang Shusen, Qi Fang, Zhang Zhonghui, Chen Jiayin, Jiang Lingli, Wang Dali, Deng Chengliang, Nie Kaiyu, Xu Guangchao, Wei Zairong
Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, No. 149 Dalian Road, Huichuan District, Zunyi, Guizhou 563003, China.
The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi medical University, No. 6 West Xuefu Road, Xinpu District, Zunyi, Guizhou, 563003, China.
Burns Trauma. 2023 Apr 27;11:tkad013. doi: 10.1093/burnst/tkad013. eCollection 2023.
Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration.
SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment.
SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and . Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells.
These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.
从间充质干细胞分化而来的雪旺细胞样细胞（SCLCs）在临床前研究中已显示出在治疗周围神经损伤方面的良好效果。然而，某些临床障碍限制了它们的应用。因此，本研究的主要目的是探讨SCLCs来源的外泌体（SCLCs-exo）在周围神经再生中的作用。
从人羊膜间充质干细胞（hAMSCs）分化出SCLCs，并通过免疫荧光、实时定量PCR和蛋白质印迹分析进行验证。通过超速离心法分离hAMSCs来源的外泌体（hAMSCs-exo）和SCLCs来源的外泌体，并通过纳米颗粒跟踪分析、蛋白质印迹分析和电子显微镜进行验证。在坐骨神经损伤大鼠模型中，使用预制神经移植物递送hAMSCs-exo或SCLCs-exo。根据神经功能的恢复情况和组织形态计量学变化，确定hAMSCs-exo或SCLCs-exo对大鼠周围神经损伤（PNI）再生的影响。还通过细胞增殖和迁移评估来确定hAMSCs-exo或SCLCs-exo对雪旺细胞的影响。
SCLCs显著表达雪旺细胞标志物胶质纤维酸性蛋白和 。与hAMSCs-exo相比，SCLCs-exo在大鼠模型中显著增强了运动功能恢复，减轻了腓肠肌萎缩，并促进了轴突再生、髓鞘形成和血管生成。此外，hAMSCs-exo和SCLCs-exo被雪旺细胞有效吸收。然而，与hAMSCs-exo相比，SCLCs-exo显著促进了雪旺细胞的增殖和迁移。SCLCs-exo还显著上调了雪旺细胞中胶质细胞源性神经营养因子、髓鞘阳性调节因子（SRY盒转录因子10、早期生长反应蛋白2和有机阳离子/肉碱转运体6）和髓鞘蛋白（髓鞘碱性蛋白和髓鞘蛋白零）的表达。
这些发现表明，SCLCs-exo比hAMSCs-exo能更有效地促进PNI再生，是一种治疗PNI的潜在新疗法。
