The leading edge: Emerging neuroprotective and neuroregenerative cell-based therapies for spinal cord injury

Abstract Spinal cord injuries (SCIs) are associated with tremendous physical, social, and financial costs for millions of individuals and families worldwide. Rapid delivery of specialized medical and surgical care has reduced mortality; however, long-term functional recovery remains limited. Cell-based therapies represent an exciting neuroprotective and neuroregenerative strategy for SCI. This article summarizes the most promising preclinical and clinical cell approaches to date including transplantation of mesenchymal stem cells, neural stem cells, oligodendrocyte progenitor cells, Schwann cells, and olfactory ensheathing cells, as well as strategies to activate endogenous multipotent cell pools. Throughout, we emphasize the fundamental biology of cell-based therapies, critical features in the pathophysiology of spinal cord injury, and the strengths and limitations of each approach. We also highlight salient completed and ongoing clinical trials worldwide and the bidirectional translation of their findings. We then provide an overview of key adjunct strategies such as trophic factor support to optimize graft survival and differentiation, engineered biomaterials to provide a support scaffold, electrical fields to stimulate migration, and novel approaches to degrade the glial scar. We also discuss important considerations when initiating a clinical trial for a cell therapy such as the logistics of clinical-grade cell line scale-up, cell storage and transportation, and the delivery of cells into humans. We conclude with an outlook on the future of cell-based treatments for SCI and opportunities for interdisciplinary collaboration in the field. Significance statement Traumatic spinal cord injuries (SCIs) result in tremendous lifelong disability and financial burden for millions of patients and caregivers worldwide. Cell-based therapies have emerged as an exciting neuroprotective and neuroregenerative strategy for SCI. This review highlights key preclinical and clinical data in cell therapy with an emphasis on the pathobiology and mechanisms of recovery. Also discussed are adjunct treatments to maximize the efficacy of the grafts. Finally, important translational considerations such as clinical-grade scale-up and delivery techniques are discussed. The article succinctly provides readers with a working knowledge of SCI and cell therapies at the leading edge of research.