Stem Cell Therapy for Locomotion Recovery and Neuropathic Pain Alleviation in Spinal Cord Injury: An Umbrella Review and Meta-Analysis Publisher Pubmed



Af Azimi Amir FARBOD ; A Toloui AMIRMOHAMMAD ; Mh Mozafarybazargany Mohammadhossein HOSSEIN ; M Kiah MOHAMMAD ; Y Sarveahrabi YASIN ; P Paridari PARSA ; S Jabermoradi SAJJAD ; D Pourkand DONYA ; Ha Ramawad Hamzah ADEL ; Ar Vaccaro Alexander R
Source: Spinal Cord Published:2025

Abstract

Study design: An Umbrella Review and Meta-analysis. Objective: This umbrella review and meta-analysis aims to evaluate the efficacy of stem cell therapy for locomotion recovery and neuropathic pain alleviation in rodent models of spinal cord injury (SCI). Methods: A comprehensive literature search was conducted in Medline, Embase, Scopus, and Web of Science until May 2024 to identify systematic reviews/meta-analyses on stem cell therapy for SCI. Original studies from these reviews were screened based on the predefined inclusion criteria. Data on locomotion, thermal hyperalgesia, and mechanical allodynia were extracted. Standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated and pooled to determine overall effect sizes. Subgroup analyses and meta-regressions were performed to investigate the optimal conditions for efficacy in each stem cell type. Results: 31 systematic reviews/meta-analyses with 323 original studies (516 experiments, 11,290 rodents) were included. Significant locomotion recovery was observed across stem cell types, with umbilical cord-derived mesenchymal stem cells (U-MSCs) (SMD = 2.34, 95% CI 1.76–2.93) and oligodendrocyte progenitor cells (OPCs) (SMD = 2.14, 95% CI 1.24–3.03) demonstrating superior efficacy. Only bone marrow-derived mesenchymal stem cells (BM-MSCs) alleviated mechanical allodynia (SMD = 1.33, 95% CI 0.61–2.05). Subgroup analysis showed that the efficacy of stem cell therapy is dependent on injury models, injury to treatment interval, stem cell dosage, and use of antibiotics/immunosuppressants. The certainty of evidence assessment showed high certainty for U-MSC in locomotion recovery, medium for BM-MSC in pain alleviation, and low for OPCs in locomotion recovery. Conclusion: With moderate-to-high certainty, our study demonstrated superior efficacy of mesenchymal stem cells, particularly U-MSCs, when administered immediately post-injury at lower doses without antibiotics for locomotion recovery and BM-MSCs for pain alleviation. These findings suggest further clinical investigation of these stem cell types under optimal conditions. (Figure presented.) © 2025 Elsevier B.V., All rights reserved.