Critical limb ischemia: Current and novel therapeutic strategies

Critical limb ischemia (CLI) is the advanced stage of peripheral artery disease spectrum and is defined by limb pain or impending limb loss because of compromised blood flow to the affected extremity. Current conventional therapies for CLI include amputation, bypass surgery, endovascular therapy, and pharmacological approaches. Although these conventional therapeutic strategies still remain as the mainstay of treatments for CLI, novel and promising therapeutic approaches such as proangiogenic gene/protein therapies and stem cell‐based therapies have emerged to overcome, at least partially, the limitations and disadvantages of current conventional therapeutic approaches. Such novel CLI treatment options may become even more effective when other complementary approaches such as utilizing proper bioscaffolds are used to increase the survival and engraftment of delivered genes and stem cells. Therefore, herein, we address the benefits and disadvantages of current therapeutic strategies for CLI treatment and summarize the novel and promising therapeutic approaches for CLI treatment. Our analyses also suggest that these novel CLI therapeutic strategies show considerable advantages to be used when current conventional methods have failed for CLI treatment. Conventional therapies critical limb ischemia (CLI) treatment encompass surgical approaches, by which the blood flow to the ischemic tissue/limb is increased. Some novel promising approaches have been shown to be effective and safe, including the application of proangiogenic gene(s) and/or protein(s), drugs, and (stem) cells such as bone marrow (BM)/peripheral blood mononuclear cells, endothelial progenitor cells, mesenchymal stem cells, and adipose‐derived stem cells (whether to be used with bioscaffolds or alone).