Cell Therapies: New Frontier for the Management of Diabetic Foot Ulceration

While stem cells hold great potential to improve existing therapies for diabetic foot ulcers, their promise has not been fully exploited. There is a critical need to further develop existing sources of adult stem cells known to improve DFU healing and to test novel, replenishing sources of pluripotent stem cells (iPSCs) that may overcome impaired wound repair when delivered to DFUs. This chapter summarizes the capacity of multiple adult stem cell sources, including bone marrow-derived mesenchymal stem cells, hematopoetic stem cells, endothelial progenitor cells, bone marrow and peripheral blood mononuclear cells, and adipose stem cells, to improve DFU healing outcomes in preclinical animal models and human clinical trials. We also review novel technologies, such as iPSC-derived cell sources, CRISPR gene editing, and 3D human tissue models, to generate and modify stem cells that can give rise to multiple cell types needed for DFU healing and to streamline their preclinical testing. By further understanding how stem cells and other new technologies can best stimulate tissue regeneration, we will be able to overcome existing barriers to improve DFU therapies.