Clinical and functional outcomes of stem cell therapy in the management of severe traumatic brain injury: a systematic review and meta-analysis

Abstract Background Stem cell therapies are increasingly explored as adjuncts for severe traumatic brain injury (TBI). This study evaluates their impact on clinical and functional outcomes. Methods A systematic search of Medline, ScienceDirect, Cochrane, and Google Scholar was conducted through April 2025 (PROSPERO CRD420251021650). Severe TBI was defined as Glasgow Coma Scale (GCS) ≤ 8. Outcomes included GCS; for adults, the National Institutes of Health Stroke Scale (NIHSS; pre‑specified as exploratory); and for pediatric cohorts, Pediatric Logistic Organ Dysfunction (PELOD), Pediatric Intensity Level of Therapy (PILOT), and Pediatric Injury Functional Outcome Scale (PIFOS). Functional measures included the Fugl‑Meyer Motor Assessment (FMMA) and Functional Independence Measure (FIM). Random‑effects meta‑analyses were performed, stratified by age cohort. Results Eleven studies comprising 275 patients (mean age 25.58 ± 7.27 years) were included. Adults demonstrated progressive GCS improvement from baseline (mean 6.06 [95% CI 4.67–7.45]) to 2 months (12.70 [10.42–14.99]), whereas pediatric patients exhibited an immediate post‑intervention decline (6.25 to 4.84) with recovery by day 21 (12.61 [11.66–13.57]). In adult cohorts, exploratory NIHSS analyses showed stepwise reductions from baseline to 2 months (MD − 17.80; 95% CI − 18.51 to − 17.09; p < 0.001). In pediatric cohorts, PELOD decreased to day 21 (MD − 5.00; 95%CI − 6.39 to − 3.61; p < 0.001) and PILOT declined from day 3 to day 21 (MD − 12.40; 95% CI − 14.58 to − 10.22; all p < 0.001). At 6 months, adults showed significant motor gains on FMMA (MD 8.40; 95% CI 0.20–16.60; p = 0.045) and a significant improvement in FIM‑Cognitive (MD 5.33; 95% CI 1.55–9.11; p = 0.006), while FIM‑Motor was non‑significant (MD 1.16; 95% CI − 0.45–2.77; p = 0.158). Complication rates varied by route ( p < 0.001), being lowest with intrathecal delivery (0.09; 95% CI 0.03–0.17). Conclusion Stem cell therapy in severe TBI was associated with time‑dependent changes in neurological and systems‑level metrics, with adult GCS and pediatric PELOD/PILOT showing improvement over time. Functional gains were evident in FMMA and FIM‑Cognitive, whereas FIM‑Motor effects were not significant.