Long-term effect of autologous progenitor cell therapy to induce neo angiogenesis in patients with critical limb ischemia transplantated via intramuscular vs combined intramuscular and distal retrograde intra venous

Abstract

Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply; this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its longterm effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29 -1.0 in group A and 0.40 -0.90 in group B; pain-free walking distance which increased at a range of 50 -600 m in group A and 50 -300 m in group B; and blood perfusion (measured by Laser Doppler) which increased at a range of 48 -299 in group A and 135 -225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.

Effect of autologous transplant of peripheral blood mononuclear cells in combination with proangiogenic factors during experimental revascularization of lower limb ischemia

“…The first surgical procedure includes a medial laparotomy and ligation of the right external iliac artery using 8‐0 suture and preserving the internal iliac artery. Then, the second surgical procedure was performed 7 days after the first procedure and consists of a vascular approach with the ligation of the deep femoral artery, where a complete excision of the superficial femoral artery was carried out (Padilla et al, ). During this latter procedure, 2 ml of blood were extracted from the cava vein to determine plasma angiogenic factors.…”

“…During the second lavage, the cava is sectioned, so the venous blood may have external flow. Lavages were performed until there was no evidence of circulating blood, evaluated visually through the cava blood flow drainage (Padilla et al, ). Then, corporectomy was executed and conventional angiography with ethiodized oil contrast media (Lipiodol Ultra‐fluide, Guerbet, France) was performed.…”