Efficacy of Fetal MSC Therapy for Osteogenesis Imperfecta: A Systematic Review and Meta-Analysis in Mice

Osteogenesis imperfecta (OI) is a genetic disorder marked by collagen defects that cause skeletal fragility. Current treatments improve bone density but not bone quality or fracture rates. Fetal mesenchymal stem cells (fMSCs) show superior osteogenic and immunomodulatory potential compared with adult mesenchymal stem cells (MSCs) and may offer a disease-modifying therapy.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically reviewed preclinical murine studies assessing the use of fMSC transplantation for OI. Data from eligible studies were pooled using random-effects meta-analysis (Hartung-Knapp adjustment). Risk ratios (RRs) were used for fracture incidence and standardized mean differences (SMDs) for mechanical and structural outcomes.

Four studies (219 mice: 91 treated, 128 controls) met inclusion criteria. fMSC treatment significantly reduced total long-bone fracture incidence (RR = 0.30; 95% confidence interval [CI]: 0.13-0.72; p = 0.027). Nonsignificant trends favored fMSC therapy for maximum load (SMD = 0.60), bone volume fraction (SMD = 0.40), cortical thickness (SMD = 0.65), and stiffness (SMD = 0.57). Heterogeneity among secondary outcomes reflected methodological variability and differences in engraftment efficiency.

fMSC transplantation significantly reduces fracture burden and shows consistent trends toward improved bone structure and strength in OI murine models. These findings support the need for further standardized, multicenter studies to optimize cell delivery, enhance engraftment, and validate clinical efficacy in humans. However, given the small evidence base, lack of independent replication, and reliance on a single OI mouse model, these findings should be interpreted as exploratory and hypothesis-generating rather than confirmatory.