Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research

Stem Cell Therapy for Diabetic Foot Ulcers: A Review of Preclinical and Clinical Research

Diabetic foot ulcers (DFUs) represent a major, hard-to-heal complication of diabetes that frequently precedes amputation and imposes a significant healthcare burden. These ulcers typically arise from a complex interplay of ischemia, infection, neuropathy, and metabolic dysfunction, which collectively impair the body's natural wound-healing processes.

Study Overview and Methodology

The authors conducted a comprehensive review of 89 studies, including both preclinical and clinical research, sourced from PubMed, EMBASE, and Google Scholar (search date November 1, 2017). While the results are promising, the authors emphasize that they are currently hard to generalize due to significant variations in cell types, sources, delivery routes, dosing, and the concurrent use of angioplasty.

Commonly Used Stem Cell Types

Nearly all reviewed studies utilized adult stem cells. The distribution of cell sources varied between research phases:

• Bone marrow–derived MSCs (BM-MSCs): The most common source in both preclinical and clinical work.

• Adipose-derived stem cells (ADSCs): Used more frequently in preclinical studies than in clinical settings.

• Peripheral blood–derived MSCs (PB-MSCs): Utilized relatively more often in clinical studies.

Clinical Evidence and Adjunct Therapies

The quality of clinical evidence is currently limited by a lack of randomized clinical trials (only 8 RCTs identified) and high heterogeneity in study design. However, certain adjuncts may improve patient outcomes:

• Angioplasty + Stem Cells: Combination therapy often reported superior vascular and wound metrics (e.g., ABI, TcPO₂) and lower restenosis rates compared to either treatment alone.

• G-CSF Mobilization: Some protocols used G-CSF for EPC mobilization, with a common regimen of 5 μg/kg twice daily for 5 days, though protocols remain inconsistent.

Safety, Limitations, and Conclusions

While generally framed as safe and effective, the review notes that delivery routes and patient factors are critical. For instance, one clinical report mentioned microthrombosis following endovascular autologous ADSC delivery as a potential risk. The paper concludes that while stem cell therapy is a viable alternative when revascularization options are limited, the field requires standardized, comparable trials to determine the optimal cell source, dosage, and delivery methods.