ACPs in Severe PAD/CLI by Direct Intramuscular Injection

Six patients with Critical Limb Ischemia (CLI) or severe Peripheral Arterial Disease(PAD) will be enrolled, screened, treated with an injection of Blood-Borne Autologous Angiogenic Cell Precursors(ACPs) in to gastrocnemius of the ischemic leg by intramuscular under regional anesthesia. Following injection.

Inclusion criteria

• Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for >2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene ; or non-healing ischemic ulcers AND
• Subjects will have one or more of the following hemodynamic indicators of severe peripheral arterial occlusive disease:

• Ankle brachial index < 0.45
• Toe brachial index < 0.35
• TcPO2 / TcO2 of < 40 mmHg.
• The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, or unfavorable anatomy
• Age 18 to 80 years
• Male or non-pregnant, non-lactating female
• Informed consent obtained and consent form signed

Exclusion criteria

• Patient having on angiography a meaningful supra popliteal occlusion that may relate to symptoms of CLI.
• Subjects, who in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment
• Patient who received blood transfusions during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood).
• Inability to communicate (that may interfere with the clinical evaluation of the patient)
• Major operation during the preceding 3 months
• Myocardial infarction or brain infarction or uncontrolled myocardial ischemia or persistent severe heart failure (EF< 25 %) during the preceding 3 months
• Significant valvular disease or after valve replacement during the preceding 3 months
• After heart transplantation
• Severe cardiomyopathy (EF < 25 %)
• Renal failure (creatinine > 2 mg/dl )
• Hepatic failure
• Anemia (lower than 11mg/dl.hemoglobin for female and lower than 12 mg/dl for male)
• Abnormal coagulation tests [platelets, PT (INR), PTT]
• Stroke within the preceding 3 years
• Malignancy within the preceding 3 years
• Concurrent chronic or acute infectious disease
• Severe concurrent medical disease (e.g., septicemia, HIV-1,2/HBV/HCV infections, poorly controlled insulin-dependent diabetes mellitus ; HBA1c >8 % and proliferative retinopathy , systemic lupus erythematosus, multiple sclerosis, amyotrophic lateral sclerosis)
• Chronic immunomodulating or cytotoxic drugs treatment
• Patients who have rectal temp. above 38.40C for 2 consecutive days
• Patient unlikely to be available for follow-up