Impaired mobilization of CD133(+) bone marrow-derived circulating progenitor cells with an increased number of diseased coronary arteries in ischemic heart disease patients with diabetes.

BACKGROUND: The influence of the number of diseased coronary arteries on the mobilization of CD133/45(+) bone marrow-derived circulating progenitor cells (BM-CPCs) in peripheral blood (PB) in patients with ischemic heart disease (IHD) was analyzed. METHODS AND RESULTS: Mobilization of CD133/45(+) BM-CPCs by flow cytometry was measured in 120 patients with coronary 1 vessel (IHD1, n=40), coronary 2 vessel (IHD2, n=40), and coronary 3 vessel disease (IHD3, n=40), and in a control group (n=40). The mobilization of CD133/45(+) BM-CPCs was significantly reduced in patients with IHD compared to the control group (P<0.001). The mobilization of CD133/45(+) BM-CPCs was impaired in patients with IHD3 compared to IHD1 (P<0.001) and to IHD2 (P<0.001). But there was no significant difference in mobilization of CD133/45(+) BM-CPCs between the patients with IHD2 and IHD1 (P=0.35). Moreover, we found significantly reduced CD133/45(+) cell mobilization in patients with a high SYNTAX-Score (SS) compared to a low SS (P<0.001) and an intermediate SS (P<0.001). In subgroup analyzes, we observed a significantly negative correlation between levels of hemoglobin A(1c) and the mobilization of CD133/45(+) BM-CPCs (P=0.001, r=-0.6). CONCLUSIONS: The mobilization of CD133/45(+) BM-CPCs in PB is impaired in patients with IHD. This impairment might augment with increased number of diseased coronary arteries. Moreover, mobilization of CD133/45(+) BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD.

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.