Exosomes as a Next-Generation Therapeutic Platform for Spinal Cord Injury: From Mechanistic Insights to Clinical Translation

Abstract

Spinal cord injury (SCI) leads to devastating neurological deficits, with its complex pathophysiology posing significant challenges for complete functional recovery. In recent years, extracellular vesicles, particularly exosomes, have emerged as a promising “cell-free” therapeutic strategy due to their crucial role in intercellular communication. This review systematically summarizes recent advances in exosome-based therapies for SCI. We first delineate the unique biological characteristics and therapeutic potential of exosomes derived from diverse sources, including mesenchymal stem cells, glial cells, and Schwann cells. We then provide an in-depth analysis of the core evidence demonstrating how exosomes, through the delivery of specific cargoes such as microRNAs, modulate multiple repair mechanisms, including neuroinflammation, apoptosis/pyroptosis, axonal regeneration, angiogenesis, and blood-spinal cord barrier integrity. Furthermore, we critically evaluate engineering strategies developed to overcome the limitations of natural exosomes, encompassing biomaterial-based delivery systems (e.g., hydrogels, scaffolds), cargo pre-modification, and synergistic interactions with traditional therapies (e.g., Chinese medicine, acupuncture). While preclinical findings are encouraging, this review also highlights significant challenges in current research regarding standardized preparation, targeting efficiency, long-term safety, and clinical translation pathways. Finally, we propose future directions involving multi-omics integration, intelligent delivery systems, and well-designed clinical trials to facilitate the transition of exosome therapies from bench to bedside.