Enhanced mobilization of the bone marrow-derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction.

Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow-derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45(+) - and CD133/45(+)-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45(+): P < 0.001, CD133/45(+): P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in PB and this might increase the regenerative potency after AMI.

Improved functional activity of bone marrow derived circulating progenitor cells after intra coronary freshly isolated bone marrow cells transplantation in patients with ischemic heart disease.

OBJECTIVES: There is growing evidence that intracoronary autologous bone marrow cells transplantation (BMCs-Tx) in patients with chronic myocardial infarction beneficially affects postinfarction remodelling. In this randomized controlled study we analyzed the influence of intracoronary autologous freshly isolated bone marrow cells transplantation by use of point of care system on cardiac function and on the functional activity of bone marrow derived circulating progenitor cells (BM-CPCs) in patients with ischemic heart disease (IHD). METHODS: 56 patients with IHD were randomized to either received freshly isolated BMC-Tx or a control group that did not receive cell therapy. The functional activity of BM-CPCs in peripheral blood (PB) was measured by migration assay and colony forming unit assay pre- and 3, 6 as well as 12 months after procedure. Global ejection fraction (EF) and infarct size area were determined by left ventriculography. RESULTS: Intracoronary transplantation of autologous freshly isolated BMCs led to a significant reduction of infarct size and an increase of global EF as well as infarct wall movement velocity after 3 and 12 months follow-up compared to control group. The colony-forming capacity of BM-CPCs significantly increased 3, 6 and 12 months after cell therapy compared to pre BMCs-Tx and control group (CFU-E: p < 0.001, CFU-GM: p < 0.001). Likewise, we found significant increase of migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) after cell therapy compared to pre BMCs-Tx (SDF-1: p < 0.001, VEGF: p < 0.001) and to control (SDF-1: p < 0.001, VEGF: p < 0.001). There was no significant difference of migratory- and colony forming capacity between pre- and 3, 6, 12 months after coronary angiography in control group without cell therapy. CONCLUSIONS: Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system may lead to improvement of BM-CPCs functional activity in peripheral blood, which might increase the regenerative potency in patients with IHD.