Therapeutic Angiogenesis by Autologous Transplantation of Bone Marrow Mononuclear Cells for Buerger's Patients with Retractable Limb Ischaemia: A Preliminary Report.

Bone marrow implantation into ischaemic limbs could enhance angiogenesis by supplying endothelialprogeniter cells and angiogenic cytokinesot factors. We investigated efficacy and safety of autologousimplantation of bonemarrow-mononuclearcells (BMMC)in patients with ischaemic limbs due to Buerger's disease. We commence daciinical 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 define das ischaemic rest painin a limb with or without non healing ulcers, should not respond to previous iloprost infusions and smoking cessation six months prior to evaluation and should not be candidates for nonsurgicalor surgical revascularisation. Primaryend points were safety andfeasibility of the treatmentand total healing of the most importantlesion. Secondary endpoints were total relief of rest pain without the need for analgesies,change in peak walkingtime (PWT)at 12 weeks, improvements in ankle-brachial pressure index(ABI), transcutaneous oxygen saturation using pulse oximetry(SaO2),angiographic evidence of newcollatera lvesselformation, tissue perfusion in the affected extremity using Thallium perfusions cintigraphyW. hilepatients(meanage46.7: !: 10.3years)were undergeneraal naesthesiaw, eharvested bonemarrow(519: t 45.5mUfromtheposteridilriacspineA. fterredbloodcell(RBCd) epletiaannd volumereduction using a continuous flow cell separator,we achieved 91% RBC depletian and concentrated /~MMC to a final volume and concentration of 51.5: t io.1 mLand7.04: t 1.9 x ioe7/mL total nucleated cells, respectively W.eimplantedBMMC (mean12.16: t 4.3 x ioe8) within three hours after marrow aspiration by intramuscular injection into the gastrocnemiusmuscle of ischaemic legs. Isotonic saline were injected into the other extremityin as similar fashion as control. 13 Unilateral intramuscular administration of BMMC was not associated with any complications. The primary efficacy end point, total healing of the most importantlesion, was achieved in three patients. All patients were followed up for at least four weeks. The secondary measures; change in PWT(LlPWT)at 12 weeks, total relief of rest pain without the need of analgesics improved in three patjents. 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 presentedstudy are promising. Thus, bone marrow maybe a potential source of cells for Buerger'spatients with end-stage Iimbischaemia refractory to other medical treatment modalities.