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.

Meta-Analysis of Cell Therapy Trials for Patients With Heart Failure

“…The primary outcomes of this Where multiple times of follow-up were reported, data were extracted for the longest possible duration of shortterm and long-term follow-up. The authors of 18 trials were contacted for clarification of data, including apparent discrepancies and insufficient detail in the reporting of methods or results 19,[22][23][24][25][26][27][28][29] or for mean and standard deviation values of outcomes where not explicitly reported 11,19,25,[30][31][32][33][34][35][36] or where reported graphically. 9,10,[37][38][39] Responses were obtained from authors of 7 trials (see Acknowledgments section).…”

“…25 The remaining 15 trials compared treatment to no treatment. 10,19,20,23,24,26,30,37,[48][49][50][51][52][53][54] Twelve trails delivered the cells via the coronary arteries (IC), 10,22,26,[28][29][30]35,[48][49][50]52,54 whereas the remaining 19 trials injected the cells into the heart muscle (IM). …”

“…included a description of the method of randomization and allocation concealment, which included computerized methods, sealed envelopes, a telephone interactive voice-response system, colored ball selection, random number tables, and site-independent randomization, and the risk of selection bias in these trials was low. In 14 trials, 10,19,26,[28][29][30]34,35,37,48,50,52,54 no method of allocation concealment was reported, and therefore, these trials were considered to have an unclear risk of selection bias because of poor allocation concealment.…”

“…In a further 14 trials, 19,24,26,28,31,32,37,42,44,48,[50][51][52][53] all outcomes mentioned in the methods were reported in the results, although it would be difficult to rule out selective reporting, and these trials were therefore considered to have an unclear risk of reporting bias. The risk of bias was also unclear in 7 other trials in which either one predefined secondary outcome was not reported, 20,34 one reported outcome was not included in the trial registration or protocol, 10,35,49 or in the case of 2 trials, 29 interim results of secondary outcomes only were presented.…”

Intra-coronary freshly isolated bone marrow cells transplantation improve cardiac function in patients with ischemic heart disease

“…We showed in pilot study that freshly isolated BMCs-Tx by use a point of care system is safe and feasible as well as may improve the cardiac function also in patients after AMI [22]. Previous studies have demonstrated, that the mobilization and functional activity of CD34/45 + and CD133/45 + BM-CPCs significantly increased after intracoronary infusion of BMCs in patients with ischemic heart disease [23][24]. We demonstrated the same results for the first time with intracoronary freshly isolated BMCs-Tx by use a point of care system in patients with IHD, not Ficoll gradient separation as in other studies.…”