Abstract

Background: Several populations of adult stem cells have been identified in bone marrow: hematopoietic stem cells, which are able to regenerate hematopoiesis in all of its lineages, mesenchymal stem cells, which can give rise to connective tissues (bone, cartilage and fat), and endothelial progenitor cells, which can initiate angiogenesis. Adult stem cells are found within the mononuclear cells compartment of bone marrow. Recent reports describe the effect of mononuclear bone marrow cells in reparation of ischemic tissue damage.

Methods: The authors designed the experimental protocol of cellular therapy for patients after acute myocardial infarction. Inclusion criteria were: first myocardial infarction treated with primary angioplasty and stent implantation, confirmed non-viability of myocardium by USG, PET and SPECT, elevated CK-MB, and age below 70 years. Patients with intervention on other coronary artery, in unstable condition at day 4 through 6, and with serious non-cardiac disease were excluded. Patients undergoing coronary angioplasty, who signed informed consent, were randomized into three arms: A - high dose of 1•108 mononuclear cells, B - low dose of 1•107 cells, C - no cells. The autologous bone marrow was collected within day 7 after infarction. The mononuclear cells were separated, cultured for 24 hours in serum-free medium, and implanted through catheter via coronary artery into the damaged heart muscle in 7 subsequent injections. Mononuclear cells were analyzed with multicolor flow cytometry and culture assays of CFU-GM and CFU-Meg. The cardiac perfusion, metabolism and function were evaluated with SPECT, PET and echocardiography at 3 months after cell implantation.

Results: 31 patients enrolled into the study underwent the protocol (9 in group A, 11 in groups B and C, respectively), and their cardiac functions were evaluated afterwards. There were no serious adverse effects of cell therapy procedure observed in each group. The analysis at 3 months interval showed an improvement in metabolism in the cellular therapy arms detected by PET. Left ventricle ejection fraction improved from 38 to 44%, although this improvement in global heart function was not statistically significant. However, regional heart function at the infarction site (peak systolic velocity of the infarcted wall) improved from 4.1 to 5.0 cm/s in the arm A (p<0.01), while no improvement was observed in arms B and C. A very significant improvement in metabolism and regional function of infarcted area of left ventricle was observed in three patients, all within the treatment arm A.

Conclusion: Mononuclear bone marrow cells as a potential source of adult stem cells can be enriched, cultured ex vivo, and safely used in the cellular therapy protocols for ischemic heart disease. The functional benefit of dose of 1•108 mononuclear cells can be detected in a group of patients after acute myocardial infarction.

This work was supported by grant IGA NR8003-3/2004.

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