Diabetic foot ulcer (DFU) is a severe complication of diabetes and a challenging medical condition. Conventional treatments for DFU have not been effective enough to reduce the amputation rates, which urges the need for additional treatment. Stem cell-based therapy for DFU has been investigated over the past years. Its therapeutic effect is through promoting angiogenesis, secreting paracrine factors, stimulating vascular differentiation, suppressing inflammation, improving collagen deposition, and immunomodulation. It is controversial which type and origin of stem cells, and which administration route would be the most optimal for therapy. We reviewed the different types and origins of stem cells and routes of administration used for the treatment of DFU in clinical and preclinical studies. Diabetes leads to the impairment of the stem cells in the diseased patients, which makes it less ideal to use autologous stem cells, and requires looking for a matching donor. Moreover, angioplasty could be complementary to stem cell therapy, and scaffolds have a positive impact on the healing process of DFU by stem cell-based therapy. In short, stem cell-based therapy is promising in the field of regenerative medicine, but more studies are still needed to determine the ideal type of stem cells required in therapy, their safety, proper dosing, and optimal administration route.
Keywords: diabetic foot ulcer (DFU); nanomaterials; peripheral artery disease (PAD); secretome; stem cell therapy.