Comparative Efficacy and Safety of Stem Cell Therapy with Standard Care in Patients with Muscular Dystrophy: A Systematic Review of Randomized Controlled Trials

OBJECTIVES: This study was aimed to address the conflict about whether stem cell therapy is effective and safe in Muscular Dystrophies (MD).

METHODS: An electronic search on Cochrane Library, Embase, PubMed, and Web of Science from inception to August 2023 to identify randomised controlled trials (RCTs) on the efficacy and safety of stem cell therapy compared to usual care in MD. Improvement in muscle strength, functional ability and quality of life (QoL) beyond 6-mo of treatment were the efficacy outcomes, while occurrence of treatment-emergent adverse events (TEAEs) were the safety outcomes. The Risk of Bias version 2 tool was applied for quality assessment of individual study, while GRADE for certainty assessment of individual outcome. The pooled estimates was reported as risk ratio(RR) with 95% confidence interval(CI) and heterogeneity (I²).

RESULTS: Three RCTs on Duchenne Muscular Dystrophy (DMD) with low risk of bias were included. The nature of stem cell therapies and route of administration included autologous transplantation of muscle-derived CD133+ stem cells in abductor digiti minimi (ADM) muscle (n=1) and allogeneic cardiosphere-derived cells (n=2, one intracoronary and one intravenous route). There was an insignificant difference in muscle force of ADM muscles between muscle-Derived CD133+ stem Cells group and the sham therapy group. At 12-mo, the improvement in performance of upper limb function (n=2), and inferior wall systolic thickening by MRI (n=1) was identified. Two trials had reported the higher numbers of TEAEs with CAP-1002 versus control (RR: 1.14; 95% CI: 0.85-1.52; I²: 0%) in DMD.

CONCLUSIONS: Considering limited RCTs and low certainty of evidence, suggest little to no difference in clinical improvement and QoL in persons with stem cell therapy among MD and highlights the necessity of larger trials, extended follow-ups, and meaningful outcomes, and meaningful outcomes to establish the potential role of stem cell therapy in MD.