Article

Intracoronary infusion of autologous bone marrow cells and left ventricular function after acute myocardial infarction: a meta-analysis.

Institute for Molecular Cardiovascular Research and Interdisciplinary Center for Clinical Research BIOMAT, RWTH University Hospital Aachen, Aachen, Germany.
Journal of Cellular and Molecular Medicine (Impact Factor: 3.7). 07/2006; 10(3):727-33. DOI: 10.1111/j.1582-4934.2006.tb00432.x
Source: PubMed

ABSTRACT Recent clinical studies have demonstrated that intracoronary infusion of autologous bone marrow cells (BMC) in conjunction with standard treatment may improve left ventricular function after an acute myocardial infarction (AMI). However, the results of these studies remain controversial, as the studies were relatively small in size and partially differed in design. We reviewed primary controlled randomized clinical studies comparing intracoronary transfer of autologous non-mobilized BMC combined with standard therapy versus standard therapy alone in patients with AMI. We identified five randomized controlled clinical trials, three of which were also placebo- and bone marrow aspiration-controlled. Non-mobilized BMC were infused into the revascularized coronary target artery 6.6 +/- 6.1 days after AMI. The mean follow- up period of 5.2 +/- 1.1 months was completed by 482 patients, 241 of which received infusion of BMC. The effect of BMC on left ventricular ejection fraction (LVEF) as a major functional parameter was evaluated. Analyzing the overall effect on the change in LVEF between baseline and follow-up value revealed a significant improvement in the BMCtreated group as compared to the control group (P = 0.04). Thus, considering the increase in LVEF during follow-up, transplantation of BMC may be a safe and beneficial procedure to support treatment of AMI. However, the functional improvement observed with this form of therapy was altogether relatively moderate and the studies were heterogeneous in design. Hence, further efforts aiming at large-scale, double-blind, randomized and placebo-controlled multi-center trials in conjunction with better definition of patients, which benefit from BMC infusion, appear to be warranted.

0 Bookmarks
 · 
39 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Studying the proliferative ability of human bone marrow derived mesenchymal stem cells in hypoxic conditions can help us achieve the effective regeneration of ischemic injured myocardium. Cardiac-type fatty acid binding protein (FABP3) is a specific biomarker of muscle and heart tissue injury. This protein is purported to be involved in early myocardial development, adult myocardial tissue repair and responsible for the modulation of cell growth and proliferation. We have investigated the role of FABP3 in human bone marrow derived mesenchymal stem cells under ischemic conditions. MSCs from 12 donors were cultured either in standard normoxic or modified hypoxic conditions, and the differential expression of FABP3 was tested by quantitative (rt)PCR and western blot. We also established stable FABP3 expression in MSCs and searched for variation in cellular proliferation and differentiation bioprocesses affected by hypoxic conditions. We identified: 1) the FABP3 differential expression pattern in the MSCs under hypoxic conditions; 2) over-expression of FABP3 inhibited the growth and proliferation of the MSCs; however, improved their survival in low oxygen environments; 3) the cell growth factors and positive cell cycle regulation genes, such as PCNA, APC, CCNB1, CCNB2 and CDC6 were all down-regulated; while the key negative cell cycle regulation genes TP53, BRCA1, CASP3 and CDKN1A were significantly up-regulated in the cells with FABP3 overexpression. Our data suggested that FABP3 was up-regulated under hypoxia; also negatively regulated the cell metabolic process and the mitotic cell cycle. Overexpression of FABP3 inhibited cell growth and proliferation via negative regulation of the cell cycle and down-regulation of cell growth factors, but enhances cell survival in hypoxic or ischemic conditions.
    Experimental Cell Research 02/2014; DOI:10.1016/j.yexcr.2014.02.015 · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Concerns regarding the use of selected bone marrow stem cells (BMSCs) in the field of cardiac repair after acute ischemic events have been raised. The current meta-analysis aimed to assess the efficacy and safety of selected BMSC transplantation in patients with acute myocardial infarction (AMI) based on published randomized controlled trials (RCTs). A systematic literature search of PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane library from 1990 to 2014 was conducted. Results from RCTs involving subjects with AMI receiving selected BMSC therapy and followed up for at least 6months were pooled. Eight trials with a total of 262 participants were included. Data were analyzed using a random effects model. Overall, selected BMSC therapy improved left ventricular ejection fraction (LVEF) by 3.17% (95% confidence interval [CI] 0.57-5.76, P=0.02), compared with the controls. There were trends toward reduced left ventricular end-systolic volume (LVESV) and fewer major adverse cardiac events (MACEs). Subgroup analysis revealed a significant difference in LVEF in favor of selected BMSC therapy with bone marrow mesenchymal stem cells (BMMSCs) as the cell type. Transplantation of selected BMSCs for patients with AMI is safe and induces a significant increase in LVEF with a limited impact on left ventricular remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 11/2014; 177(3):764-770. DOI:10.1016/j.ijcard.2014.11.005 · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: La thérapie par cellules progénitrices après un infarctus du myocarde (IM) est un domaine prometteur des recherches translationnelles. Malgré une compréhension mécaniste limitée, plusieurs essais aléatoires et contrôlés ont été effectués auprès d’environ 400 patients peu après un IM, par l’administration de cellules progénitrices circulantes ou dérivées de la moelle osseuse. Jusqu’à présent, l’expérience indique une amélioration modeste mais significative de la fraction d’éjection ventriculaire gauche à un degré comparable à celui des thérapies classiques courantes après un IM. Même si certaines études ont donné des résultats négatifs, il faut tenir compte de problèmes comme le traitement des cellules, le moment de la livraison et la puissance de l’étude ainsi que du fait que les analyses systématiques de l’ensemble des publications étayent les bienfaits globaux de cette thérapie. Il faudra confirmer ces observations dans des études clés de phase 3, mais même une amélioration modeste de la fonction cardiaque après un IM peut avoir des répercussions cliniques importantes, notamment chez les patients ayant subi un infarctus plus étendu. De plus, il est possible que l’on remarque des bienfaits cliniques plus robustes grâce à des stratégies visant à isoler des populations cellulaires plus actives et à vaincre les effets délétères des facteurs de risque cardiovasculaires sur la fonction des cellules progénitrices autologues. Des modes de traitement plus raffinés des cellules, couplés à des essais cliniques bien conçus, pourraient contribuer à transformer le domaine de la thérapie par cellules progénitrices en intervention adjuvantes efficace après un IM.
    The Canadian journal of cardiology 08/2008; 24:5C–10C. DOI:10.1016/S0828-282X(08)71030-4 · 3.12 Impact Factor

Preview

Download
1 Download