Diabetic foot ulcers (DFUs) are among the most common and costly complications of diabetes, and a substantial proportion fail to heal despite standard care of offloading, debridement, infection control, and revascularization when indicated. This persistent burden has driven interest in cell-based therapies, particularly mesenchymal stem cells (MSCs), which are thought to promote repair through paracrine signalling, angiogenesis, and modulation of chronic inflammation. Two recent meta-analyses and the 2023 IWGDF guideline provide a useful picture of where the evidence stands.
Why Stem Cells Have Been Studied in Diabetic Wounds
Chronic diabetic wounds are characterized by impaired angiogenesis, persistent inflammation, and dysfunctional fibroblasts and keratinocytes. Stem cells can be harvested from several sources, including bone marrow, peripheral blood, adipose tissue, and umbilical cord, and may be delivered by local injection, topical application, or cell sheets. Because the sources, doses, and delivery methods differ so widely between trials, comparing studies is difficult, and this variability is a recurring theme in the literature.
What Recent Meta-Analyses Report
Cell source and healing rate
Tong and colleagues (2025) pooled 24 studies including 1,321 patients, with searches run to October 2024. Stem cell therapy was associated with a higher likelihood of wound healing overall (odds ratio 4.40, 95% CI 3.23–5.99), which fell to 3.40 (95% CI 2.39–4.84) after adjustment for publication bias. Estimates differed by cell source, with odds ratios of 7.31 for peripheral blood, 5.23 for adipose, and 4.36 for bone marrow–derived cells. Healing time was shorter by roughly 13 days, although heterogeneity for that outcome was extremely high (I² = 99%). The authors concluded that stem cell therapy is promising but called for larger confirmatory studies.
Adipose-derived stem cells in randomized trials
Abu Elainein and colleagues (2025) restricted their analysis to randomized controlled trials of adipose-derived stem cells (ADSCs). Six trials with 316 participants were included. ADSCs were associated with a higher rate of complete healing (risk ratio 1.56, 95% CI 1.32–1.86) and a shorter time to healing (mean difference −19.3 days), though the latter had very low certainty because of heterogeneity. Reported adverse events were minor, such as haematoma at the harvest site and wound infection, and no immune reactions were described in the allogeneic studies. Cost data were limited and inconsistent: one trial reported higher costs with ADSC therapy, while another found no significant difference.
Limitations of the Evidence
Several caveats apply to both analyses. Trials were generally small, ranging from about a dozen to roughly 100 participants. Standard care differed across studies, blinding was often incomplete, and cell preparation and dosing were not standardized. Tong and colleagues identified publication bias, which tends to inflate apparent benefit. Meta-analyses of small, heterogeneous trials can therefore produce large pooled effect sizes that may not be reproduced in large, well-controlled studies. Longer-term outcomes that matter most to patients, such as ulcer recurrence, major amputation, and quality of life, remain poorly reported.
Where Guidelines Stand
The 2023 IWGDF guideline on interventions to enhance healing of foot ulcers in diabetes (Chen and colleagues, Diabetes/Metabolism Research and Reviews, 2024) emphasizes that adjunctive therapies should be considered only when good standard care has not produced healing. The adjuncts it supports conditionally, such as sucrose octasulfate dressings, placental-derived products, autologous leucocyte/platelet/fibrin patches, topical and hyperbaric oxygen, and negative pressure wound therapy for post-operative wounds, are recommended with the acknowledgement that overall certainty of evidence is low. Stem cell therapy is not among these recommendations, which reflects the early stage of the evidence base rather than evidence of harm.
Clinical Summary
Stem cell–based therapies show consistent signals of improved healing in small trials and meta-analyses, with a generally acceptable short-term safety profile for adipose-derived cells. However, heterogeneity, small sample sizes, publication bias, and limited cost and long-term data mean that these therapies remain investigational relative to established standard care. Optimal cell source, dose, delivery route, and patient selection are still undefined. Offloading, perfusion assessment, infection control, and glycemic management remain the foundation of DFU healing, and adjunctive cell therapy is best understood as an area of active research.
References
- Tong L, Tang L, Tang B, Zhang J. Impacts of stem cells from different sources on wound healing rate in diabetic foot ulcers: a systematic review and meta-analysis. Frontiers in Genetics. 2025.
- Abu Elainein MA, Allam S, et al. Therapeutic potential of adipose-derived stem cells for diabetic foot ulcers: a systematic review and meta-analysis. Diabetology & Metabolic Syndrome. 2025;17:9.
- Chen P, Vilorio NC, Dhatariya K, et al. Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes/Metabolism Research and Reviews. 2024;40(3):e3644.
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