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      Direct minimally invasive intramyocardial injection of bone marrow-derived AC133+ stem cells in patients with refractory ischemia: preliminary results.

      The Thoracic and cardiovascular surgeon
      Aged, Angina Pectoris, therapy, Antigens, CD, Female, Glycoproteins, Hematopoietic Stem Cell Mobilization, Humans, Injections, Male, Mesenchymal Stem Cell Transplantation, Middle Aged, Myocardial Ischemia, Neovascularization, Physiologic, Organophosphorus Compounds, diagnostic use, Organotechnetium Compounds, Peptides, Pilot Projects, Radiopharmaceuticals, Tomography, Emission-Computed, Single-Photon, Transplantation, Autologous

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          Abstract

          Bone marrow-derived stem cells (BMSC) may represent a viable option for patients with myocardial ischemia refractory to conventional treatments. In 5 patients (4 males and 1 female, mean age 64 +/- 8 years) with untreatable angina pectoris (Canadian Cardiovascular Society Class III/IV), myocardial segments with stress-induced ischemia as assessed by gated single-photon emission computed tomography were injected with 4 to 12 million CD133+ BMSC. Cells were injected into the myocardium (2 anterior, 2 lateral, 1 inferior wall) through minimally invasive approaches (left minithoracotomy [n = 4] and subdiaphragmatic approach [n = 1]). At baseline, at 6 months and at 1 year of follow-up, an exercise test, gated single-photon emission computed tomography (SPECT), 2-D echocardiography and coronary angiography were performed to assess exercise capacity, myocardial perfusion, LV function and coronary anatomy. Intramyocardial injection of autologous CD133+ BMSC cells was safe. No early or long-term complications were observed. After an average of 3.8 weeks from cell inoculation, all patients experienced a significant improvement of CCS class (from 3.8 to 1.8 at 6 months) and serial SPECT documented improvements of rest and stress perfusion in the injected territories at 6 months from operation. In 3 cases, coronary angiography showed an increase in the collateral score of the target areas. Clinical improvements still persist unchanged in 4 out of 5 cases at a mean of 36.5 months postoperatively. After stand-alone BMSC transplantation for refractory myocardial ischemia, we observed long-term clinical and perfusion improvements in the absence of adverse events.

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