Innovations in Stem Cell Therapy for Diabetic Wound Healing.

Significance: The global burden of diabetic wounds, particularly diabetic foot ulcers, continues to have large economic and social impact throughout the world. Current strategies are not sufficient to overcome this burden of disease. Finding newer, more advanced regenerative cell and tissue-based strategies to reduce morbidity remains paramount. Recent Advances: Recent advances in stem cell therapies are discussed. We also highlight the practical issues of translating these advancing technologies into the clinical setting. Critical Issues: We discuss the use of somatic and induced pluripotent stem cells and the stromal vascular fraction, as well as innovations, including the use of 3D bioprinting of skin. We also explore related issues of using regenerative techniques in clinical practice, including the current regulatory landscape and translatability of in vivo research. Future Directions: Advances in stem cell manipulation showcase the best therapeutic resources available to enhance mechanisms of wound healing such as angiogenesis, cell proliferation, and collagen synthesis; potential methods include changing the scaffold microenvironment, including relative oxygen tension, and the use of gene modification and nanotechnology. Secretome engineering, particularly the use of extracellular vesicles, may be another potential cell-derived therapeutic that may enable use of cell-free translational therapy.