Stem Cell-Based Therapies for Chronic Wound Healing: Current Evidence and Future Perspectives

Abstract

Background: Chronic wounds, including diabetic foot ulcers, venous leg ulcers, and ischemic wounds, fail to progress through the normal phases of healing and impose a substantial clinical and economic burden. Stem cell-based therapies, principally mesenchymal stem cells (MSCs) and their derivatives, have been investigated as regenerative alternatives to conventional wound management.
Objective: To critically appraise current clinical and mechanistic evidence for stem cell-based therapies in chronic wound healing, compare outcomes across cell sources and wound aetiologies, and examine the regulatory and safety considerations governing their translation into practice.
Data Sources: PubMed/MEDLINE, Scopus- and Web of Science-indexed journals, and publications from Frontiers, MDPI, Springer Nature, Wiley, PLOS, and SAGE were searched for literature published predominantly between 2019 and 2026, supplemented by landmark earlier studies and current US Food and Drug Administration (FDA) regulatory guidance.
Review Methods: A comprehensive narrative review format was adopted to accommodate the methodological breadth of the field, spanning mechanistic, preclinical, clinical trial, and regulatory literature. Evidence was appraised for study design, cell source, and outcome measures, with emphasis on comparing findings across wound aetiologies rather than sequential summarisation.
Key Findings: Meta-analyses of randomised controlled trials indicate that MSC-based therapy improves ulcer healing rate and reduces amputation risk in diabetic foot ulcers relative to conventional care, with evidence certainty rated low to moderate by GRADE criteria. Evidence in venous leg ulcers and critical limb ischemia remains limited to small, mostly phase I/II trials. Cell-free MSC-derived extracellular vesicles and induced pluripotent stem cell (iPSC)-derived lineages show mechanistic promise but remain confined chiefly to preclinical and early translational studies. Regulatory classification under the US FDA’s 351/361 framework materially determines the evidentiary and manufacturing burden applicable to a given product, and tumorigenicity and manufacturing variability remain unresolved safety considerations for pluripotent-derived cells.
Conclusion: Stem cell-based therapies, particularly MSC-based interventions, show reproducible benefit for diabetic foot ulcer healing in randomised trials, while evidence for other chronic wound types and for cell-free and pluripotent-derived approaches remains preliminary. Continued translation should be paced to standardised manufacturing, long-term safety follow-up, and harmonised regulatory classification.