Intrathecal versus intravenous umbilical cord mesenchymal stem cells for ischemic stroke sequelae

Abstract Background Stroke is a leading cause of death worldwide. Traditional treatments have limitations, stem cell therapy has potential for regeneration after ischemic stroke. This study evaluated the safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell (UC-MSC) infusion via the intravenous (IV) and intrathecal (IT) routes for treating neurological sequelae after ischemic stroke. Methods This phase II randomized controlled trial involved 32 patients aged 40–75 years with neurological sequelae after ischemic stroke. The patients were randomly assigned into two groups: 16 received two IT UC-MSC infusions plus rehabilitation therapy, and 16 received two IV UC-MSC infusions plus rehabilitation therapy. Additionally, 16 matched controls, paired with the IT group by sex, age (±5 years), and NIHSS, received only rehabilitation. UC-MSCs were administered at 1.5 × 106 cells/kg at baseline and 3 months. Outcomes were assessed at baseline, 3, 6, and 12 months using NIHSS, FIM, MAS, FMS, and SF-36. Results No severe adverse events related to UC-MSC therapy were observed. Adverse event rate was lower in the IV group than the IT group. At 6 months, the IV group demonstrated significant improvements in NIHSS (p = 0.046), FIM (p = 0.028), and SF-36 (p 0.001). At 12 months, both UC-MSC groups showed significant improvements, with greater effects in the IV group (p 0.001 for SF-36). Conclusion Both IV and IT UC-MSC infusions improved neurological recovery and quality of life, with fewer adverse events in the IT group. Trial registration NCT05292625