Regenerative Medicine in Critical Limb Ischemia

—Current and Future Directions

Abstract

Critical limb ischemia (CLI) is commonly caused by atherosclerotic arterial obstruction or stenosis in the leg, as demonstrated by rest pain, skin ulcers and gangrene (Fontaine III or IV), often fails to respond to conservative treatments, and carries a high risk for limb amputation, with a particularly dismal prognosis. Although surgical revascularization techniques may be used for certain CLI patients, such techniques are not indicated for most CLI patients due to the diffuse nature of the responsible lesions, distal location of the obstruction, or coexisting systemic comorbidities. For such CLI patients with no alternative treatments, the potential utility of cell therapies has been investigated. Indeed many clinical trials are being carried out by academic sectors, and their achievements will facilitate clinical development by pharmaceutical companies.
In order to understand the situation regarding competitive international R&D of revascularization seeds for CLI, we surveyed the status of clinical trials. As a result, we identified 58 clinical trials on revascularization for CLI, with the majority in the early phase (<phase II: 82.7%). Revascularization seeds for CLI are in the development and competition phase, and promising seeds are expected to appear in the near future.
In this review, we discuss how to develop optimal regenerative medicine concerning the selection of cell origin, cell type, combination with growth factor, and the influence of concomitant disease.