No effective blood-flow enhancement therapies are available for patients with severe peripheral arterial disease (SPAD), thus amputation remains the only option for relief of rest pain or gangrene. Autologous bone marrow-derived stem cell therapy (ABMSCT) is an emerging modality to induce angiogenesis from endothelial progenitors. Eight lower limbs of seven patients with SPAD (seven limbs of six patients with Buerger’s disease) were treated by ABMSCT using isolated CD34+ cells with characterized phenotype and administered by intramuscular injections. The follow-up before and 1-, 3-, 6-, 9- and 12 months after ABMSCT was based on clinical (rest pain, walking distance without pain, non-healing ulcers, ABI) and laboratory (DS-angiography, duplex- and laser ultrasonography, TcPO2) measurements. Therapeutic benefit was demonstrated by complete regression of rest pain in all of the 7 patients, and by the significant improvement of pain-free walking distance (40 m vs 500 m). The average of ABI improved significantly on the treated (before:0.41, after twelve months: 0.83), but did not change on the contralateral limb. Non-healing ischemic ulcers disappeared in five, and became smaller and thinner in two lower limbs, the ulcer remained unchanged in one case, only. The clinical improvement started one month after ABMSCT, it became more prominent after at three months, and the best clinical results were observed after twelve months of the stem cell therapy. In all of the seven cases we observed improvement on the treated limb only, the contra-lateral symptoms and ulcers remained unchanged or worsened. Confirmed by posttrial observations obtained at 18 months after ABMSCT the clinical improvement was evaluated as stable and long lasting. New collaterals were detected by angiography in three patients, but duplex ultrasonography detected improvement in two patients only. Laser ultrasonography did not show significant changes whereas TcPO2 values improved on the foot from 18.80/16.78/23.83 mmHg, and on the calf from 36.66/31.25/45.00 mmHg. These laboratory parameters did not show improvement after 1 month, however, after 6 and 12 months improved values were recorded. Severe adverse events, complications were not observed. We conclude that ABMSCT with isolated CD34+ cells is safe, effective, localized and results in local and sustained clinical benefit for patients with severe forms of Buerger’s disease. We show for the first time that low number of isolated bone marrowderived CD34+ stem cells that involve CD34+CD133+, CD34+CD133−, CD34+CD45− and CD34+CD45+ cells with different vessel forming ability confers vasculogenesis upon intramuscular implantation to patients with Buerger’s disease.

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