From neural stem cells to cell-free exosome nanotherapy: reprogramming the injured spinal cord microenvironment for regeneration

Abstract

Spinal cord injury (SCI) is a severely disabling neurological disorder with a global prevalence of approximately 10.5 cases per 100,000 individuals. The pathophysiological mechanisms underlying SCI encompass both primary mechanical trauma and a series of secondary injury processes, which ultimately result in enduring neurological deficits and significant socioeconomic challenges. Existing treatment modalities-including pharmacological, surgical, and rehabilitative approaches-exhibit limited effectiveness in facilitating functional recovery. Recently, neural stem cells (NSCs) and exosomes derived from these cells have emerged as innovative therapeutic options with substantial promise. NSCs facilitate neural repair through their ability to undergo multipotent differentiation, secrete neurotrophic factors, and modulate the immune response within the injury microenvironment. However, their clinical translation is hampered by poor graft survival, ethical constraints, and risks of immune rejection. In contrast, NSC-derived exosomes represent a promising cell-free alternative, delivering bioactive molecules-such as miRNAs and proteins-that suppress neuroinflammation, attenuate glial scarring, enhance axonal regeneration, and promote angiogenesis. With favorable attributes including low immunogenicity, high biocompatibility, and non-tumorigenic properties, exosome-based therapies offer a transformative approach for overcoming current limitations in SCI treatment.