Efficacy and safety of mesenchymal stem cell transplantation for progressive multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials with clinical implications for patient stratification and treatment optimization

Why clinicians should know about it

• Picked for Transplantation (top studies of the week, 9 August 2026): MSC for multiple sclerosis, not transplant

Abstract

BACKGROUND: Progressive multiple sclerosis (PMS) is a disabling demyelinating disease characterized by irreversible neurodegeneration. Unlike relapsing-remitting MS, for which many disease-modifying therapies exist, treatment options for PMS are extremely limited. Only two agents (ocrelizumab and siponimod) have modest efficacy, and no effective therapies exist for non-active disease. Mesenchymal stem cell (MSC) transplantation has emerged as a promising strategy due to its immunomodulatory and neurotrophic properties. However, clinical trials have yielded inconsistent results, and prior meta-analyses were limited by mixed MS subtypes and non-randomized studies, leaving uncertainty about MSC's clinical utility in PMS. OBJECTIVE: To rigorously evaluate the efficacy and safety of MSC transplantation in PMS patients through a systematic review and meta-analysis of exclusively randomized controlled trials (RCTs), and to provide evidence-based recommendations. METHODS: Two researchers searched PubMed, Embase, Web of Science, Cochrane Library, and Chinese databases from inception to March 2026. RCTs comparing MSC transplantation with placebo in adult PMS patients were included. Primary outcome: change in Expanded Disability Status Scale (EDSS) score. Secondary outcomes: treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Meta-analysis used RevMan 5.4 with random/fixed-effects models. Certainty of evidence was assessed by GRADE. Protocol registered on PROSPERO (CRD420261301154). RESULTS: Three RCTs (143 patients; 75 MSC, 68 control) were included. MSC therapy did not significantly improve EDSS scores (pooled MD = -0.08, 95% CI -0.38 to 0.22, P = 0.61; I² = 66%). MSC did not increase TEAEs (RR = 1.08, 95% CI 0.86 to 1.35, P = 0.52) or SAEs (RR = 0.79, 95% CI 0.26 to 2.36, P = 0.67). GRADE: moderate certainty for TEAEs, very low for EDSS change and SAEs. CONCLUSION: MSC transplantation appears safe in PMS patients, with no increased adverse event risk. However, current evidence does not support significant benefit on EDSS scores in unselected patients. Given the very low to moderate certainty, further high-quality RCTs are warranted.This systematic review and meta-analysis was conducted in strict accordance with the Cochrane Handbook for Systematic Reviews of Interventions (version 6.5) and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines[24, 25]. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration number: CRD420261301154) prior to literature screening and data extraction.

Abstract as published, via PubMed.