Stem and Somatic Cell Monotherapy for the Treatment of Diabetic Foot Ulcers: Review of Clinical Studies and Mechanisms of Action.

Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus, often resulting in a limb amputation. A cell-based therapy is a highly promising approach for an effective DFU treatment. However, there is no consensus regarding the most effective cell type for DFU treatment. Various cell types contribute to chronic wound healing via different mechanisms. For example, application of keratinocytes can stimulate migration of native keratinocytes from the wound edge, while mesenchymal stem cells can correct limb ischemia. To assess the effectiveness of a certain cell type, it should be administered as a monotherapy without other substances and procedures that have additional therapeutic effects. In the present review, we described therapeutic effects of various cells and provided an overview of clinical studies in which stem and somatic cell-based therapy was administered as a monotherapy. Topical application of somatic cells contributes to DFU healing only, while injection of mesenchymal stem cells and mononuclear cells can break a pathophysiological chain leading from insufficient blood supply to DFU development. At the same time, the systemic use of mesenchymal stem cells carries greater risks. Undoubtedly, cell therapy is a potent tool for the treatment of DFU. However, it is vital to conduct further high-quality clinical research to determine the most effective cell type, dosage and way of administration for DFU treatment. Ischemia, neuropathy and neuro-ischemia are underlying factors of diabetic foot ulcer. Stem and somatic cells monotherapy can improve chronic wound healing via different mechanisms.