The prognosis for postinjury peripheral nerve regeneration remains suboptimal. Although transplantation of exogenous Schwann cells (SCs) has been considered a promising treatment to promote nerve repair, this strategy has been hampered in practice by the limited availability of SC sources and an insufficient postengraftment cell retention rate. In this study, to address these challenges, SCs were aggregated into spheroids before being delivered to an injured rat sciatic nerve. We found that the three-dimensional aggregation of SCs induced their acquisition of a repair phenotype, as indicated by enhanced levels of c-Jun expression/activation and decreased expression of myelin sheath protein. Furthermore, our in vitro results demonstrated the superior potential of the SC spheroid-derived secretome in promoting neurite outgrowth of dorsal root ganglion neurons, enhancing the proliferation and migration of endogenous SCs, and recruiting macrophages. Moreover, transplantation of SC spheroids into rats after sciatic nerve transection effectively increased the postinjury nerve structure restoration and motor functional recovery rates, demonstrating the therapeutic potential of SC spheroids. In summary, transplantation of preassembled SC spheroids may hold great potential for enhancing the cell delivery efficiency and the resultant therapeutic outcome, thereby improving SC-based transplantation approaches for promoting peripheral nerve regeneration.

中文翻译：

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雪旺细胞在组装成球体后获得修复表型，并显示出增强的促进周围神经修复的体内治疗潜力

损伤后周围神经再生的预后仍然不理想。尽管外源雪旺细胞 (SC) 移植被认为是促进神经修复的一种有前景的治疗方法，但该策略在实践中因 SC 来源有限和移植后细胞保留率不足而受到阻碍。在这项研究中，为了解决这些挑战，SCs 在被输送到受伤的大鼠坐骨神经之前被聚集成球体。我们发现 SC 的三维聚集诱导其获得修复表型，如 c-Jun 表达/激活水平增强和髓鞘蛋白表达减少所示。此外，我们的体外结果表明，SC 球体来源的分泌蛋白组在促进背根神经节神经元的神经突生长、增强内源性 SC 的增殖和迁移以及招募巨噬细胞方面具有卓越的潜力。此外，在坐骨神经横断后将SC球体移植到大鼠体内，有效提高了损伤后神经结构恢复和运动功能恢复率，证明了SC球体的治疗潜力。总之，预组装 SC 球体的移植可能具有提高细胞递送效率和最终治疗结果的巨大潜力，从而改进基于 SC 的移植方法以促进周围神经再生。