Keywords
hUC-MSC
Diabetic Foot
Exosomes
Healing
Scoping Review
How to Cite
Abstract
Introduction. Diabetic foot ulcers (DFUs) represent a severe and debilitating complication of diabetes mellitus, often proving refractory to conventional therapies due to a persistent pro-inflammatory state that delays granulation tissue formation and re-epithelialization. While stem cell therapies offer potential, challenges regarding tumorigenicity, cell survival, and regulatory hurdles have spurred interest in cell-free approaches, specifically nanometric vesicles known as exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs). This scoping review aimed to map the extent and nature of evidence regarding the therapeutic application of hUC-MSC-derived exosomes in diabetic wound management across preclinical and clinical settings.
Methods. Conducted according to the Joanna Briggs Institute (JBI) methodology and PRISMA-ScR guidelines, systematic searches were performed in PubMed, Embase, CINAHL, Lilacs, and grey literature (Google Scholar and Research Square) through January 31, 2026.
Results. Nineteen studies met the inclusion criteria, primarily comprising preclinical investigations (n=15) alongside two randomized clinical trials. Preclinical evidence consistently demonstrates that hUC-MSC-derived exosomes accelerate wound closure by enhancing angiogenesis (CD31 and VEGF upregulation), modulating macrophage polarization toward the anti-inflammatory M2 phenotype, and promoting extracellular matrix restructuring. Clinical trials involving 130 participants reported favorable outcomes, including complete ulcer closure and a documented safety profile over a 24-month follow-up period. Technological advancements include the use of biomaterial carriers, such as hydrogels and scaffolds, to ensure sustained release and localized retention within the wound bed.
Discussion. While evidence is consistent in the preclinical domain, a significant translational gap remains due to mechanistic differences between rodent contraction-based healing and human re-epithelialization. Standardizing dose-response protocols and conducting multicenter randomized trials are essential to bridge the gap toward real-world clinical implementation.
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