Clinical Evidence of Mesenchymal Stromal Cells for Cerebral Palsy: Scoping Review with Meta-Analysis of Efficacy in Gross Motor Outcomes.

Abstract

Mesenchymal stromal cells (MSCs) have been under clinical investigation for the treatment of cerebral palsy (CP) for over a decade. However, the field has been limited by study heterogeneity and variable reports of efficacy. We conducted a scoping review of published and registered reports of MSC treatment for CP, with meta-analysis of Gross Motor Function Measure (GMFM) outcomes to summarize research and provide future recommendations. Thirty published reports and 10 registered trials were identified, including 1292 people with CP receiving MSCs. Most received ≥2 doses (72%) of umbilical cord tissue MSCs (75%), intrathecally (40%) or intravenously (38%), and 31% were treated via compassionate/Expanded access. MSC treatment was safe and meta-analyses demonstrated that MSCs conferred significant improvements in GMFM at 3 - (1.05 (0.19-1.92), p = 0.02), 6 - (0.97 (0.30-1.64), p = 0.005) and 12 months (0.99 (0.30-1.67), p = 0.005) post-treatment. Whilst MSCs are safe and improve GMFM outcomes in CP with large effect sizes, study and participant variability continues to confound data interpretation and limits subgroup analyses. With no published Phase 3 trials and high rates of compassionate access, the field would benefit from well-designed trials with unified outcomes. Additionally, data sharing to enable Individual Participant Data Meta-Analysis would support the determination of optimal source, route and dose to progress towards regulatory approval.