Peripheral artery disease is caused by obstructing atherosclerotic plaques that critically reduce blood flow during exercise. The disease affects ≈4% of people >40 years and 15% to 20% of subjects above 65 years of age. Critical limb ischemia, the most severe manifestation of peripheral artery disease, describes patients with chronic ischemic rest pain, or patients with ischemic skin lesions, either ulcers or gangrene. It requires foot amputation in 25% of cases within 1 year from the diagnosis. Revascularization therapies are indicated in critical limb ischemia patients, but they are often ineffective or unfeasible; and in the latter case, the reported amputation and mortality rates exceed 50%. Therefore, new therapeutic approaches are urgently needed.