Combination Autologous Peripheral Blood-Derived Stem Cell/Progenitor Cell (Cd34+) Stem Cells and Hyperbaric Oxygen Therapy for the Treatment of Severe Limb Ischemia: Investigate the Safety and Efficacy

Original Hypothesis: This study (phase I clinical trial) will test the hypothesis that combined CD34+ cells and hyperbaric oxygen (HBO) therapy will be safe and effective for peripheral arterial occlusive disease (PAOD) patients. Background: Atherosclerosis are results endothelial dysfunction, progressive and complex inflammatory process and proliferation of arterial smooth muscle layer that affect both regional and systemic arteries. PAOD caused by atherosclerotic lesions is an important manifestation of systemic atherosclerosis. Patients with PAOD may develop critical limb ischemia (CLI) at the late stage of the disease propagation. Actually, CLI represents the most advanced PAOD with a severe obstruction of the arteries which markedly reduces blood flow to the extremities and has progressed to the point of severe rest pain and/or even tissue loss. Clinical observational studies have established that without appropriate and aggressive treatment, the one-year mortality rate has been reported to be as high as 25%. Failure in salvaging CLI can lead to major limb loss and high cost of patient care following amputation. Additionally, although surgical or endovascular revascularization have been used for the treatment of CLI with acceptable successful rate, for the patients who are not well suited for surgical or endovascular intervention and those with failure of revascularization or bypass occlusion, the clinical outcomes remain dismal. Therefore, an alternative strategy for the treatment of such CLI patients is necessary. Recent therapeutic strategies have focused on restoring blood flow/regeneration of the microvasculature in ischemic area using cell therapy to promote favor of tissue regeneration. The results of our phase I clinical trial (由衛福部月同意進行) has recently shown that CD34+ cell therapy was safe and efficacious in improving heart function for patients with severe diffuse coronary artery disease unsuitable for coronary intervention and with poor response to pharmacotherapy. Additionally, HBO therapy has been found to improve the blood flow in limb ischemic area mainly through the enhancing generations of NO/hypoxia inducible factor (HIF)-1α, endothelial progenitor cell (EPC) homing, vasodilatation and increases in capillary/microvasculature permeability as well as anti-inflammatory effect. Rationale and aims: Thus, we propose that combined HBO and peripheral blood-derived stem cell/progenitor cell (CD34+) cells is a safe procedure and would offer additional benefit for improving ischemic leg perfusion sufficiently to reduce major amputations and permit durable limb salvage in PAOD patients who are refractory to conventional treatment.

Project ID:PC10708-0971
External Project ID:MOST107-2314-B182-070