Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing

Nonhealing diabetic foot ulcers (DFUs) are a continuing clinical issue despite the improved treatment with wound debridement, off-loading the ulcer, medication, wound dressings, and preventing infection by keeping the ulcer clean. Wound healing is associated with granulation tissue formation and angiogenesis favoring the wound to enter the resolution phase of healing followed by healing. However, chronic inflammation and reduced angiogenesis in a hyperglycemic environment impair the normal healing cascade and result in chronically non-healing diabetic foot ulcers. Promoting angiogenesis is associated with enhanced wound healing and using vascular endothelial growth factors has been proven beneficial to promote neo-angiogenesis. However, still, nonhealing DFUs persist with increased risks of amputation. Regenerative medicine is an evolving branch applicable in wound healing with the use of stem cells to promote angiogenesis. Various studies have reported promising results, but the associated limitations need in-depth research. This article focuses on summarizing and critically reviewing the published literature since 2021 on the use of stem cells to promote angiogenesis and enhance wound healing in chronic non-healing DFUs.