Stem cell therapy for traumatic brain injury: Current advances, clinical challenges, and future directions

The severity of traumatic brain injury (TBI) and its poor prognosis underscore the urgent need for more effective neuroprotective and neuroregenerative strategies. However, the pathological heterogeneity of TBI continues to hinder clinical therapeutic progress. Preclinical studies have shown that neural stem cells, through their regenerative and secretory properties, can suppress neuroinflammation and promote angiogenesis, synaptic regeneration, and neural circuit remodeling. On one hand, stem cell transplantation has entered clinical trials and demonstrates neuroprotective effects by promoting regeneration at the injury site. However, reliable evidence supporting its clinical benefits in severe TBI remains limited. Large-scale randomized controlled trials are needed to determine the optimal route, dosage, timing, and cell type for transplantation. On the other hand, emerging cell-free therapies and stem cell–scaffold combination strategies offer new directions for TBI treatment. This narrative review systematically explores recent advances, current developments, and ongoing challenges in stem cell therapy for TBI. It also highlights innovative approaches that integrate tissue engineering and genetic modification, which may drive transformative progress in TBI treatment through interdisciplinary collaboration.