Autologous transplantation of mononuclear bone marrow cells in patients with acute myocardial infarction: the effect of the dose of transplanted cells on myocardial function. Am Heart J. 152(5):975.e9-15
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.
"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.
Cardiology Research and Practice 02/2012; 2012(2090-8016):240497. DOI:10.1155/2012/240497
"There are no consensus or good meta-analysis 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 (Obradović 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.
Frontiers in Physiology 01/2012; 3:6. DOI:10.3389/fphys.2012.00006 · 3.53 Impact Factor
"Studying stem cells in experimental models (Reddy et al., 2008) by means of molecular imaging (Lucignani, 2007) may give an answer to questions related to trafficking, homing, engraftment, differentiation, and reconstruction in target tissues and optimization of these parameters (Frangioni and Hajjar, 2004; Meluzin et al., 2006; Muller-Ehmsen et al., 2006; Wang et al., 2006). For this reason, in vivo imaging and quantification of stem cells is an essential tool. "
[Show abstract][Hide abstract] ABSTRACT: Studies on stem cell are rapidly developing since these cells have great therapeutic potential for numerous diseases and has generated much promise as well as confusion due to contradictory results. Major questions in this research field have been raised as to how and in which numbers stem cells home to target tissues after administration, whether the cells engraft and differentiate, and what their long-term fate is. To answer these questions, reliable in vivo tracking techniques are essential. In vivo molecular imaging techniques using magnetic resonance imaging, bioluminescence, and scintigraphy have been applied for this purpose in experimental studies. The aim of this review is to discuss various radiolabeling techniques for early stem cell tracking, the need for validation of viability and performance of the cells after labeling, and the routes of administration in experimental animal models. In addition, we evaluate current problems and directions related to stem cell tracking using radiolabels, including a possible role for their clinical implementation.
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