Current evidence on umbilical cord and bone marrow stem cell therapy in TBI: A scoping review for future clinical practice.

Background: Traumatic brain injury (TBI) is a major global cause of long-term disability and death, with current treatments offering limited neurological recovery. Stem cell-based therapies have emerged as promising regenerative approaches. Among them, umbilical cord-derived stem cells (UC-SCs) and bone marrow-derived stem cells (BM-SCs) are frequently explored. This systematic review evaluates and compares the safety, efficacy, and outcomes of UC-SCs and BM-SCs in human TBI patients. Methods: A comprehensive search was conducted through March 2025 in PubMed, ScienceDirect, Cochrane Library, and SpringerLink using relevant keywords. Studies involving TBI patients treated with either UC-SCs or BM-SCs were included, encompassing randomized controlled trials (RCTs), cohort studies, and case reports. The JBI Critical Appraisal Tool was used to assess the risk of bias, and a narrative synthesis was performed. Results: Fifteen clinical studies involving 552 patients were included: 3 RCTs, 10 cohort studies, and 2 case reports. BM-SC therapy showed notable improvements in motor recovery, white matter integrity, and inflammation reduction, particularly in acute and subacute TBI. In contrast, UC-SC therapy demonstrated greater benefits in chronic TBI, including enhanced cognition, reduced spasticity, and improved quality of life. UC-SCs also had a favorable safety profile with a lower risk of immune rejection. No direct head-to-head trials comparing both stem cell types were found. Conclusion: UC-SC and BM-SC therapies both show promise in TBI treatment, with distinct advantages based on injury phase and therapeutic goals. BM-SCs may be more effective in acute TBI due to anti-inflammatory properties, while UC-SCs appear more suitable for chronic TBI, supporting neuroregeneration. Further direct comparative studies and standardized protocols are needed to refine stem cell therapy for TBI.