Mesenchymal Stromal/Stem Cells in Chronic Incomplete Traumatic Spinal Cord Injury: A Phase I/II Double-Blind Placebo-Controlled Multicentre Trial

Background/Objectives: Chronic traumatic spinal cord injury (SCI) causes persistent neurological deficits for which no clinically effective regenerative therapy is currently available. Mesenchymal stromal/stem cells (MSCs), particularly Wharton’s jelly-derived MSCs (WJ-MSCs), demonstrate immunomodulatory and neurotrophic potential. This phase I/II study evaluated the safety and efficacy of intrathecal allogeneic WJ-MSC administration in individuals with chronic incomplete cervical SCI. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial (NCT05054803, EudraCT 2021-000346-18), 18 participants with chronic (1–5 years post-injury) incomplete cervical SCI (AIS B–D) received two intrathecal injections of WJ-MSCs (0.7–1.3 × 106 viable cells/kg) or a placebo at baseline and 3 months. Seventeen participants completed the 12-month follow-up. Primary outcomes assessed safety, and secondary endpoints included International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and sensory scores, spasticity, neuropathic pain, functional independence, neurophysiological measures, and quality of life. Results: Intrathecal WJ-MSC administration was safe and well tolerated. Eighty adverse events occurred (placebo: 26; WJ-MSC: 54), predominantly mild or moderate; four severe events were unrelated to treatment. Both groups demonstrated significant within-group improvements in total motor scores at 12 months, with no between-group difference. No treatment effects were observed for sensory scores, electrophysiological measures, functional independence, spasticity, pain, or patient-reported outcomes. Conclusions: In this first randomised, placebo-controlled trial evaluating intrathecal WJ-MSCs in chronic incomplete cervical SCI, WJ-MSC administration demonstrated a favourable safety profile; however, no significant between-group differences were detected relative to the placebo. Given the limited sample size and early-phase design, the efficacy findings should be interpreted cautiously. Future research should explore enhanced cell products, intensified dosing schedules, optimised delivery strategies, early intervention, and multimodal therapeutic combinations.