Efficacy of Mesenchymal Stem Cells in the Treatment of Diabetic Foot Ulcers: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background

Diabetic foot ulcers (DFUs), a severe chronic complication of diabetes, are characterized by refractory wounds and high risks of amputation/mortality, posing substantial public health challenges. Mesenchymal stem cells (MSCs) demonstrate therapeutic potential through synergistic mechanisms including paracrine signaling, immunomodulation, neovascularization, and tissue regeneration. This study conducts a systematic review and meta-analysis of randomized controlled trials (RCTs) to comprehensively evaluate the clinical efficacy of MSC-based therapy for DFUs, aiming to optimize treatment strategies with evidence-based insights.

Method

We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for RCTs investigating MSC therapy in DFUs. Following PRISMA guidelines, studies were selected with pre-defined criteria. Meta-analyses employed random-/fixed-effects models based on I² statistics. Primary endpoints encompassed complete healing rate (100% epithelialization), amputation incidence, serious adverse events (SAEs) risk, and recurrence rate. Furthermore, sensitivity analyses were conducted to evaluate the robustness of the findings. A comprehensive assessment of potential publication bias in the current meta-analysis was performed using Egger's linear regression test, Begg's rank correlation test, and funnel plot visualization.

Results

Six RCTs were included. MSC therapy significantly improved overall complete healing rates (RR = 1.63, 95% CI: 1.23-2.16; P = .0007), particularly in small ulcers (<5 cm²; RR = 1.71, 1.11-2.63, P = .02), but showed no efficacy for large ulcers (≥5 cm²; RR = 1.18, 0.75-1.86, P = .46). No significant differences emerged in amputation risk (P = .16), serious adverse events (P = .38), and recurrence (P = .33). Low heterogeneity and no publication bias were observed.

Conclusion

This meta-analysis demonstrates MSCs therapy significantly enhances wound closure in diabetic foot ulcers, particularly achieving in small ulcers. However, no stable therapeutic benefits were observed for large ulcers, amputation prevention, recurrence reduction, and SAEs. Future multicenter phase III trials with standardized protocols are warranted to establish ulcer stage/size-specific treatments.