Spinal cord injury (SCI) remains a devastating neurological condition with limited therapeutic options, presenting a significant unmet medical need. This review examines the evolving landscape of mesenchymal stem/stromal cell (MSC) and MSC-derived extracellular vesicle (MSC-EV) therapies for SCI treatment. We explore the biological properties of MSCs, including their immunomodulatory capacity and secretome, and evaluate preclinical evidence demonstrating their efficacy in promoting functional recovery through blood-spinal cord barrier repair, neuroprotection, and immunomodulation. The review highlights the paradigm shift from cellular to vesicular approaches, with MSC-EVs emerging as promising cell-free alternatives that maintain therapeutic benefits while offering advantages in safety, storage, and targeted delivery. Clinical translation progress is assessed, including outcomes from recent trials showing safety and potential efficacy of MSC therapies in human SCI patients. Despite promising results, significant challenges remain in standardization, potency testing, and manufacturing of MSC-EV therapies. Future research should focus on optimizing isolation protocols, enhancing potency assays, and identifying specific EV subpopulations with targeted therapeutic effects. This review provides critical insights into current knowledge and future directions for developing these regenerative approaches to improve SCI patient outcomes.
Masahito Nakazaki (Thu,) studied this question.