The molecular profile and ability to promote axon regeneration after peripheral nerve injury by Repair Schwann cells is distinctly different from that for developing Schwann cells

Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.鉴于雪旺细胞（Schwann cells, SCs）在发育阶段及周围神经损伤（peripheral nerve injury, PNI）后均可支持轴突生长，发育阶段的雪旺细胞或可促进周围神经损伤后的轴突再生。本研究旨在阐明发育阶段雪旺细胞诱导周围神经损伤后轴突再生的能力。研究将雪旺细胞前体细胞（SC precursors, SCPs）、未成熟雪旺细胞（immature SCs, ISCs）、损伤神经来源的修复型雪旺细胞（repair SCs, RSCs）以及未损伤神经来源的非修复型雪旺细胞，移植至经压榨性损伤的大鼠坐骨神经无细胞区域以开展功能验证。实验结果显示，两类发育阶段雪旺细胞均完全无法支持轴突再生，而成熟雪旺细胞尤其是修复型雪旺细胞可有效诱导轴突再生。进一步研究表明，修复型雪旺细胞可促进成年背根神经节神经元的神经突起生长，雪旺细胞前体细胞则无此效果。转录组分析结果显示，修复型雪旺细胞与雪旺细胞前体细胞的基因表达谱存在显著差异。上述研究结果表明，发育阶段雪旺细胞与成熟雪旺细胞在功能及分子层面均存在显著差异，修复型雪旺细胞可作为周围神经损伤再生细胞治疗的潜在候选方案。