Allogeneic Mesenchymal Stromal Cell-Based Therapies for Diabetic Foot Ulcers: Systematic Review and Meta-Analysis of Controlled Topical and Local Delivery Trials

Abstract

Background: Diabetic foot ulcers are a major cause of infection, hospitalization and lower-extremity amputation worldwide. Despite advances in wound care, many ulcers fail to heal, prompting investigation of regenerative biologic strategies. Allogeneic Mesenchymal Stromal Cell (MSC)-based therapies have emerged as an adjunctive approach intended to enhance wound repair through immunomodulatory, pro-angiogenic and tissue-regenerative effects.

Objective: To evaluate controlled clinical trial evidence for allogeneic MSC-based therapies administered topically and/or by local injection for improving healing outcomes in diabetic foot ulcers, with emphasis on complete ulcer closure.

Methods: A systematic review was conducted to identify controlled clinical trials evaluating allogeneic MSC-based interventions for diabetic foot ulcers compared with standard wound care, placebo, or control dressings. Eligible delivery methods included topical application (cell sheets, hydrogels, dressings) and local injection (perilesional or intralesional). The primary endpoint was complete ulcer closure at approximately 8 to 12 weeks. Secondary outcomes included wound area reduction, time to closure, amputation, recurrence when reported and adverse events. Outcomes were synthesized under a random effects framework with consideration of heterogeneity related to cell source and delivery method.

Results: Controlled trials evaluating allogeneic MSC-based therapies demonstrated higher rates of complete ulcer closure and greater wound area reduction compared with control care. Benefits were most consistent for objective wound healing endpoints, while effects on amputation outcomes were less certain due to limited event reporting. No clear signal of increased serious treatment-related adverse events was identified.

Conclusion: Controlled clinical trial evidence suggests that allogeneic MSC-based therapies delivered topically and/or locally as an adjunct to standard wound care may improve diabetic foot ulcer healing outcomes compared with control care. Larger randomized trials with standardized ulcer classification, uniform wound care protocols and consistent outcome reporting are needed to define optimal cell source, delivery strategy and durability of ulcer closure.