Cell Therapy for Spinal Cord Injury: Mechanistic Insights and Translational Challenges

Spinal cord injury (SCI) causes devastating and permanent neurological disability, with no restorative treatments currently available. Cell-based therapies have long been regarded as the most promising regenerative strategy, demonstrating robust functional improvement in preclinical models. However, clinical outcomes have been inconsistent, exposing a persistent translational gap. This review critically appraises leading cell therapy platforms, ranging from mesenchymal and neural stem cells to next-generation engineered tissues. We dissect the molecular mechanisms underlying therapeutic efficacy and analyze key translational barriers, including GMP manufacturing, potency assay development, and clinical trial design. Integrating lessons from past failures with emerging advances in imaging biomarkers and immune-microenvironment modulation, we propose a strategic roadmap framed by a “renovate-and-rebuild” paradigm. We identify timing-by-mechanism mismatches and inadequate scar remodeling as central drivers of variable efficacy, and introduce a biomarker-gated indication algorithm to align therapies with lesion biology. Collectively, these insights argue for reframing SCI repair as a staged, biology-matched process rather than a single-shot intervention.