Abstract
Background/AimsThe progression and development of congestive heart failure is still considered a large problem despite the existence of revascularization therapies and optimal, state-of-the-art medical services. An acute myocardial infarction (AMI) is a major cause of congestive heart failure, so researchers are investigating techniques to complement primary percutaneous coronary intervention (PCI) or thrombolytic therapy to prevent congestive heart failure after AMI.MethodsTwenty-six patients with successful PCI for acute ST-segment elevation anterior wall myocardial infarction were assigned to either a control group (n = 12) or a bone marrow mesenchymal stem cells (BM-MSC) group (n = 14). The control group received optimum post-infarction treatment, and the BMSC group received intracoronary delivery of autologous BMSC at 1 month after PCI with the optimum medical treatment. The primary endpoint was a left ventricular ejection fraction (LVEF) change from baseline to 4-month follow-up, as determined via myocardial single-photon emission computed tomography (SPECT).ResultsThe global LVEF at baseline (determined 3.5 ± 1.5 days after PCI) was 35.4 ± 3.0% in the control group and 33.6 ± 4.7% in the BM-MSC group. BMSC transfer enhanced left ventricular systolic function primarily in anterior wall myocardial segments adjacent to the LAD infarcted area. Four months later, via SPECT, global LVEF had increased by 4.8 ± 1.9% in the control group and 8.8 ± 2.9% in the BM-MSC group (p = 0.031). The cell transfer did not increase the risk of adverse clinical events, in-stent restenosis, or proarrhythmic effects. The echocardiographic evaluation also revealed a significant increase in the LVEF value from baseline to the 4-month (9.0 ± 4.7 and 5.3 ± 2.6%, p = 0.023) and 12-month (9.9 ± 5.2% and 6.5 ± 2.7%, p = 0.048) follow-up in the BM-MSC group but not in the control group.ConclusionsIntracoronary administration of autologous BM-MSC was tolerable and safe with significant improvement in LVEF at 4-month (SPECT and echocardiography result) and 12-month (echocardiography result only) follow-up in patients with anterior AMI.
Highlights
Rapid reperfusion of the infarct-related coronary artery is of great importance to salvage ischemic myocardium and limit the infarct size in patients with acute myocardial infarction (AMI)
The pleiotropic mechanism of therapeutic mesenchymal stem cells (MSCs) was assayed by measuring the angiogenic effect of MSC-secreted factors including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) (Fig. 2)
MSC culture media induced human vascular endothelial cell (HUVEC) proliferation was reduced by the neutralizing antibodies against VEGF, IL-6, MCP-1 but not by hepatocyte growth factor (HGF) or transforming growth factor-beta (TGF-β)
Summary
Rapid reperfusion of the infarct-related coronary artery is of great importance to salvage ischemic myocardium and limit the infarct size in patients with acute myocardial infarction (AMI). The loss of viable myocardium initiates an adverse process of left ventricular remodelling, leading to chamber dilatation and contractile dysfunction in many patients. In this respect, stem cell therapy has emerged as a novel alternative to repair damaged myocardium. Many experimental studies have shown that cardiac transfer of un-fractionated bone marrow cells or mesenchymal stem cells (MSCs) and progenitor cells derived from bone marrow can enhance functional recovery after AMI [2, 3]. Results from clinical data [11] and from pre-clinical studies [12] have indicated the possibility of improving the therapeutic effect by using bone marrow-derived mesenchymal stem cells (BM-MSC) rather than un-fractionated bone marrow cells to treat AMI
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