Autologous cell therapy in diabetes-associated critical limb ischemia: From basic studies to clinical outcomes (Review)

Cell therapy is becoming an attractive alternative for the treatment of patients with no-option critical limb ischemia (CLI). The main benefits of cell therapy are the induction of therapeutic angiogenesis and neovascularization that lead to an increase in blood flow in the ischemic limb and tissue regeneration in non-healing cutaneous trophic lesions. In the present review, the current state of the art of strategies in the cell therapy field are summarized, focusing on intra-operative autologous cell concentrates in diabetic patients with CLI, examining different sources of cell concentrates and their mechanisms of action. The present study underlined the detrimental effects of the diabetic condition on different sources of autologous cells used in cell therapy, and also in delaying wound healing capacity. Moreover, relevant clinical trials and critical issues arising from cell therapy trials are discussed. Finally, the new concept of cell therapy as an adjuvant therapy to increase wound healing in revascularized diabetic patients is introduced.