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

Abstract

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.

FIG. 1.

(A, B) The mobilization of BM-CPCs was analyzed immediately pre- and post- and at 3, 6, and 12 months postprocedure in both groups. CD34/45⁺ and CD133/45⁺ BM-CPC mobilization significantly increased at 3, 6, and 12 months after BMCs-Tx compared with baseline, whereas no significant differences were observed between immediately pre- and postprocedure in both groups. There were no significant changes in the mobilization of BM-CPCs at 3, 6, and 12 months after coronary angiography compared with baseline in the control group without cell therapy. Moreover, there were significant differences of BM-CPC mobilization at 3, 6, and 12 months after procedure between both groups. BM-CPCs, bone marrow-derived circulating progenitor cells; BMC-Tx, bone marrow cell transplantation; WBCs, white blood cells. Color images available online at www.liebertonline.com/scd

FIG. 2.

(A–C) Global EF, infarct size, and the wall movement velocity of the infarcted area were measured by left ventriculography immediately pre-and at 3 and 12 months postprocedure in both groups. There were no significant baseline differences in global EF, infarct size, and infarct wall movement velocity between the two groups. Global EF and infarct wall movement velocity significantly increased at 3 and 12 months after cell therapy when compared with the control group. Further, there was a significant decrease of infarct size at 3 and 12 months after cell transplantation when compared with the control group. No significant changes were observed in global EF, infarct size, and infarct wall movement velocity at 3 and 12 months after coronary angiography compared with baseline in the control group without cell therapy. Further, there were significant changes in global EF, infarct size, and infarct wall movement velocity at 3 and 12 months after procedure between both groups. EF, ejection fraction. Color images available online at www.liebertonline.com/scd

FIG. 3.

(A, B) To determine the functional status of patients, NYHA classification and BNP levels were measured at 3, 6, and 12 months after procedure in both groups. There were no significant differences of baseline NYHA classification and BNP level in both groups. At 3, 6, and 12 months after cell therapy, there was a significant decrease of NYHA classification and BNP level compared with baseline. In the control group without cell therapy, there were no significant changes in NYHA classification and BNP level at 3, 6, and 12 months after coronary angiography compared with baseline. Moreover, significant differences in NYHA classification and BNP level were observed at 3, 6, and 12 months after procedure between both groups. NYHA, New York Heart Association; BNP, brain natriuretic peptide. Color images available online at www.liebertonline.com/scd