Akademik Veri Yönetim Sistemi
Turkish Journal of Haematology, cilt.21, sa.1, ss.13-21, 2004 (SCI-Expanded)
Bone marrow implantation into ischaemic limbs could enhance angiogenesis by supplying endothelial progenitor cells and angiogenic cytokines or factors. We investigated efficacy and safety of autologous implantation of bone marrow-mononuclear cells (BMMC) in patients with ischaemic limbs due to Buerger's disease. We commenced a clinical study to test cell therapy with autologous BMMC in patients with ischaemic limbs at the University of Ankara School of Medicine. In order for the patients to qualify for BMMC implantation, they should have critical limb ischaemia defined as ischaemic rest pain in a limb with or without nonhealing ulcers, should not respond to previous iloprost infusions and smoking cessation six months prior to evaluation and should not be candidates for nonsurgical or surgical revascularisation. Primary endpoints were safety and feasibility of the treatment and total healing of the most important lesion. Secondary endpoints were total relief of rest pain without the need for analgesics, change in peak walking time (PWT) at 12 weeks, improvements in ankle-brachial pressure index (ABI), transcutaneous oxygen saturation using pulse oximetry (SaO2), angiographic evidence of new collateral vessel formation, tissue perfusion in the affected extremity using Thallium perfusion scintigraphy. While patients (mean age 46.7 ± 10.3 years) were under general anaesthesia, we harvested bone marrow (519 ± 45.5 mL) from the posterior iliac spine. After red blood cell (RBC) depletion and volume reduction using a continuous flow cell separator, we achieved 91% RBC depletion and concentrated BMMC to a final volume and concentration of 51.5 ± 10.1 mL and 7.04 ± 1.9 × 10e7/mL total nucleated cells, respectively. We implanted BMMC (mean 12.16 ± 4.3 × 10e8) within three hours after marrow aspiration by intramuscular injection into the gastrocnemius muscle of ischaemic legs. Isotonic saline were injected into the other extremity in a similar fashion as control. Unilateral intramuscular administration of BMMC was not associated with any complications. The primary efficacy end point, total healing of the most important lesion, was achieved in three patients. All patients were followed up for at least four weeks. The secondary measures; change in PWT (ΔPWT) at 12 weeks, total relief of rest pain without the need of analgesics improved in three patients. These improvements were sustained for 24 weeks in the first two patients. Digital subtraction angiographic studies before and 3 months after the BMMC implantation showed the presence of a new vascular collateral network across the affected arteries in three patients. Preliminary results of the presented study are promising. Thus, bone marrow may be a potential source of cells for Buerger's patients with end-stage limb ischaemia refractory to other medical treatment modalities.