Plasticity, injury-induced reprogramming, and translational applications of Schwann cells in neural regeneration

Schwann cells (SCs), the predominant glial cell population in the peripheral nervous system (PNS), have undergone a paradigm shift from historically passive structural components of myelinated axons to active, multifunctional regulators of neural development, regeneration, and neuropathology. This review briefly outlines Schwann cell developmental origin as a biological backdrop, while centering on their inherent phenotypic plasticity and translational applications. Following peripheral nerve injury, SCs rapidly undergo context-dependent dedifferentiation and transcriptional reprogramming, acquiring a regenerative phenotype characterized by phagocytic activity, secretion of neurotrophic factors, and structural reorganization into Büngner bands. Notably, both endogenous and exogenously delivered SCs demonstrate capacity to migrate into lesioned central nervous system (CNS), including spinal cord injury sites, where they contribute to remyelination, modulation of glial scar formation, and partial restoration of electrophysiological connectivity and behavioral function. These attributes collectively establish SCs as phenotypically adaptable cellular mediators capable of facilitating neural repair across anatomically and functionally distinct compartments. To inform translational efforts, this review critically evaluates emerging strategies, including autologous cell transplantation and SC-derived exosomes, by appraising their mechanisms, limitations, and future perspectives. This review aims to deepen the mechanistic understanding of Schwann cell biology and provide a theoretical basis for the development of regenerative treatments for peripheral nerve injury and spinal cord injury.