Restoring neuroplasticity after CNS trauma: cell therapy approaches in spinal cord and traumatic brain injury

BACKGROUND: The central nervous system (CNS) has a limited regenerative capacity, rendering traumatic injuries such as spinal cord injury (SCI) and traumatic brain injury (TBI) highly disabling and difficult to treat. These insults trigger complex pathophysiological cascades, including extensive cell death, sustained inflammation, and the formation of a hostile inhibitory microenvironment that compromises neural plasticity and hampers tissue regeneration. The multifactorial nature of these mechanisms, together with a fragmented understanding of CNS plasticity, has hindered the development of effective therapeutic interventions. MAIN BODY: In recent years, cell-based therapies have emerged as promising strategies to support neural repair and induce pro-regenerative processes. This approach encompasses multiple cell types, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived stem cells (ASCs), umbilical cord mesenchymal stem cells (UCMSCs), as well as neural progenitor cells (NPCs) and olfactory ensheathing cells (OECs). Clinical studies in SCI have reported functional improvements, particularly following treatment with BMSCs and peripheral blood-derived stem cells, although substantial methodological heterogeneity limits definitive conclusions. In TBI, clinical evidence remains more limited; however, preclinical studies consistently demonstrate the neuroprotective and regenerative potential of mesenchymal stem cell-based therapies. Beyond direct cell transplantation, increasing attention has been given to cell-free approaches, including secretome and extracellular vesicle-based strategies, which recapitulate many of the beneficial effects while potentially overcoming safety and logistical constraints. CONCLUSIONS: Overall, both cell-based and cell-free therapeutic strategies show significant potential to enhance neuroplasticity, attenuate secondary injury, and promote functional recovery following CNS trauma. Nevertheless, successful clinical translation will require larger, well-controlled trials and the establishment of standardized protocols addressing optimal timing, dosage, and routes of administration.