Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: The effect of the dose of transplanted cells on myocardial function

ArticleinAmerican heart journal 152(5):975.e9-15 · November 2006with8 Reads
DOI: 10.1016/j.ahj.2006.08.004 · Source: PubMed
Abstract
Despite the reports on successful treatment of acute myocardial infarction using autologous mononuclear bone marrow cell transplantation, many unresolved questions still remain. We studied the impact of the dose of transplanted cells on myocardial function and perfusion. Sixty-six patients with a first acute myocardial infarction were randomized into 3 groups. Two groups were intracoronarily given mononuclear bone marrow cells in either higher (10(8) cells, higher cell dose [HD] group, n = 22) or lower (10(7) cells, lower cell dose [LD] group, n = 22) doses. Twenty-two patients without cell transplantation served as a control (C) group. At 3 months of follow-up, the baseline peak systolic velocities of longitudinal contraction of the infarcted wall of 5.2, 4.5, and 4.3 cm/s in C, LD, and HD groups increased by 0.0, 0.5 (P < .05 vs C group), and 0.9 cm/s (P < .05 vs LD group, P < .01 vs C group), respectively, as demonstrated by Doppler tissue imaging. Baseline left ventricular ejection fractions of 42%, 42%, and 41% in C, LD, and HD groups increased by 2%, 3%, and by 5% (P < .05 vs group C), respectively, as assessed by the gated technetium Tc 99m sestamibi single photon emission computed tomography. Mononuclear bone marrow cell transplantation improves regional myocardial function of the infarcted wall in a dose-dependent manner.
    • "Ang Assmus et al 2006 Cao et al 2009 Grajek et al 2010 Hendrikx et al 2006 Herbots et al 2009 Huikuri et al 2008 Janssens et al 2006 Lipiec et al 2009 Lunde et al 2006 Meluzin et al 2006 Meyer et al 2006 Nogueira et al 2009 Penicka et al 2007 Piepoli et al 2010 Pokushalov et al 2010 Quyyumi et al 2011 Ramshorst et al 2009 Ruan et al 2005 Srimahachota et al 2011 Suarez de Lezo et al 2007 Traverse et al 2010 Traverse et al 2011 Tse et al 2007 Turan et al 2011(b) Wohrle et al 2010 Yao et al 2009 "
    [Show abstract] [Hide abstract] ABSTRACT: Despite rapid clinical translation and widespread enthusiasm, the therapeutic benefits of adult bone marrow cell (BMC) transplantation in patients with ischemic heart disease continue to remain controversial. A synthesis of the available data is critical to appreciate and underscore the true impact of this promising approach. A total of 50 studies (enrolling 2625 patients) identified by database searches through January 2012 were included. Weighted mean differences for changes in left ventricular (LV) ejection fraction, infarct size, LV end-systolic volume, and LV end-diastolic volume were estimated with random-effects meta-analysis. Compared with control subjects, BMC-treated patients exhibited greater LV ejection fraction (3.96%; 95% confidence interval, 2.90-5.02; P<0.00001) and smaller infarct size (-4.03%, 95% confidence interval, -5.47 to -2.59; P<0.00001), LV end-systolic volume (-8.91 mL; 95% confidence interval, -11.57 to -6.25; P<0.00001), and LV end-diastolic volume (-5.23 mL; 95% confidence interval, -7.60 to -2.86; P<0.0001). These benefits were noted regardless of the study design (randomized controlled study versus cohort study) and the type of ischemic heart disease (acute myocardial infarction versus chronic ischemic heart disease) and persisted during long-term follow-up. Importantly, all-cause mortality, cardiac mortality, and the incidence of recurrent myocardial infarction and stent thrombosis were significantly lower in BMC-treated patients compared with control subjects. Transplantation of adult BMCs improves LV function, infarct size, and remodeling in patients with ischemic heart disease compared with standard therapy, and these benefits persist during long-term follow-up. BMC transplantation also reduces the incidence of death, recurrent myocardial infarction, and stent thrombosis in patients with ischemic heart disease.
    Full-text · Article · Jun 2012
    • "In subacute scenario, cells can be delivered during PCI or CABG. Since more than 90% of cells are lost after transplantation, cell therapy requires a large quantity of cells (more than 100 milions with bone marrow cells) to make up for losses and show an improvement of LVEF [14, 69]. Also, the modest improvement of function and geometry of the heart with cell therapy may necessitate the investigation of the other long-term end-points as symptom relief (angina) or major cardiac events rather than cardiac remodelling. "
    [Show abstract] [Hide abstract] ABSTRACT: Myocardial infarction is the leading cause of death in developed countries. Cardiac cell therapy has been introduced to clinical trials for more than ten years but its results are still controversial. Tissue engineering has addressed some limitations of cell therapy and appears to be a promising solution for cardiac regeneration. In this review, we would like to summarize the current understanding about the therapeutic effect of cell therapy and tissue engineering under purview of functional and structural aspects, highlighting actual roles of each therapy towards clinical application.
    Full-text · Article · Feb 2012
    • "There are no consensus or good metaanalysis to reveal whether small or large infarct are more likely to benefit from stem cell therapy. Of the three largest clinical BMC trials (Lunde et al., 2006; Meluzín et al., 2006; Schachinger et al., 2006b ), only REPAIR-AMI trial indicated that baseline EF correlated with EF change (p = 0.04) but the statistical analysis did not taken autocorrelation of the parameters into account, which should be considered as a major limitation. However, recent observations from small studies showed that large infarcts were less likely to get benefit from BMC therapy (Obradovi´cObradovi´c et al., 2009; Traverse et al., 2010). "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage. Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.4 h after symptoms) for STEMI were randomized for BMC therapy (2.9 × 10(6) CD34+ cells) or placebo after bone marrow aspiration in a double-blind, multi-center study. Three days post-MI, coronary angioplasty, and paclitaxel eluting stent implantation preceded either BMC or placebo therapy. Cardiac PET and MRI studies were performed 7-12 days after therapies and repeated after 6 months, and images were analyzed at a central core laboratory. Results: In BMC-treated patients, there was a decrease in [(11)C]-HED defect size (-4.9 ± 4.0 vs. -1.6 ± 2.2%, p = 0.08) and an increase in [(18)F]-FDG uptake in the infarct area at risk (0.06 ± 0.09 vs. -0.05 ± 0.16, p = 0.07) compared to controls, as well as less left ventricular dilatation (-4.4 ± 13.3 vs. 8.0 ± 16.7 mL/m(2), p = 0.12) at 6 months follow-up. However, BMC treatment was inferior to placebo in terms of changes in rest perfusion in the area at risk (-0.09 ± 0.17 vs. 0.10 ± 0.17, p = 0.03) and infarct size (0.4 ± 4.2 vs. -5.1 ± 5.9 g, p = 0.047), and no effect was observed on ejection fraction (p = 0.37). Conclusion: After the acute phase of STEMI, BMC therapy showed only minor trends of long-term benefit in patients with rapid successful thrombolysis. There was a trend of more decrease in innervation defect size and enhanced glucose metabolism in the infarct-related myocardium and also a trend of less ventricular dilatation in the BMC-treated group compared to placebo. However, no consistently better outcome was observed in the BMC-treated group compared to placebo.
    Full-text · Article · Jan 2012
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