Improvement of cardiac function by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction.

BACKGROUND: We analyzed in the present study the influence of intracoronary autologous freshly isolated bone marrow cells transplantation (BMCs-Tx) on cardiac function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The 32 patients with AMI were enrolled in this prospective nonrandomized study to either freshly isolated BMC-Tx or to a control group without cell therapy. Global left ventricular ejection fraction (LVEF) and the size of infarct area were determined by left ventriculography. We observed in patients with autologous freshly isolated BMCs-Tx at 6 months follow up a significant reduction of infarct size as compared to control group. Moreover, we found a significant increase of LVEF as well as infarct wall movement velocity at 6 months follow up in cell therapy group as compared to control group. In the control group there was no significant difference of LVEF, infarct size and infarct wall movement velocity between baseline and 6 months after AMI. CONCLUSIONS: These results demonstrate for the first time that intracoronary transplantation of autologous freshly isolated BMCs by use of a point of care system is safe, and may lead to improvement of cardiac function in patients with AMI.

Improved mobilization of the CD34(+) and CD133(+) bone marrow-derived circulating progenitor cells by freshly isolated intracoronary bone marrow cell transplantation in patients with ischemic heart disease.

Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45(+) and CD133/45(+) CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45(+) and CD133/45(+) BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45(+) and CD133/45(+) BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45(+) and CD133/45(+) BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD.

[Effects of exercise training on mobilization of BM-CPCs and migratory capacity as well as LVEF after AMI]. / Die Effekte von körperlichem Training auf die Mobilisation und funktionelle Aktivität zirkulierender Progenitorzellen aus dem Knochenmark sowie die LVEF nach akutem Myokardinfarkt.

BACKGROUND AND PURPOSE: Bone marrow-derived circulating progenitor cells (BM-CPCs) are mobilized in adult peripheral blood (PB) during the acute myocardial infarction (AMI) period and contribute to the regeneration of infarcted myocardium. In this study, the influence of physical training on the mobilization and the migratory activity of the BM-CPCs as well as on the left ventricular function (LVEF) after AMI was examined. PATIENTS AND METHODS: 26 patients with AMI were analyzed in two groups. The first group comprised 17 patients with standardized exercise training for 3 weeks 14 +/- 4 days after AMI, the second group nine control subjects without exercise training. PB concentrations of CD34/45+ and CD133/45+ were measured by FACS. The migratory activity of BM-CPCs was analyzed by migration assay. B-type natriuretic peptide (BNP) in PB and the functional investigations spiroergometry (VO2 and PaO2) and stress echocardiography (LVEF) were determined in both groups. RESULTS: A significant increase in both concentrations, CD34/45+ and CD133/45+, as well as in migratory capacity of BM-CPCs was found after 3 weeks of exercise training, which was significantly decreased 3 months after completion of exercise training. No significant difference was observed in the control group without exercise training. In the functional investigations a significant increase in VO2 as well as PaO2 was shown spiroergometrically after exercise training. There was no difference in stress echocardiographic LVEF at rest in both groups. On the other hand, interestingly, the findings showed that the increase of LVEF at peak stress was significantly higher after exercise training as compared to the control group. Moreover, a significant decrease in BNP values was found after exercise training as well as 3 months after AMI. No difference was found in the control group. CONCLUSION: This study demonstrates that exercise training for 3 weeks after AMI leads to a significant mobilization as well as increase of functional activation of BM-CPCs in humans. Moreover, regular exercise training might contribute to the positive effects on the regenerative potency after AMI.