Intracoronary Bone Marrow Stem Cell Research Articles

Short-Term Effect of Autologous Bone Marrow Stem Cells to Treat Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Clinical Trials.

Bone marrow stem cells (BMSCs) have been used to treat patient with ST-segment elevation myocardial infarction (STEMI) via intracoronary route. We performed a meta-analysis to evaluate the short-term efficacy and safety of this modality. Seventeen randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered with 9 days of reperfusion and followed up shorter than 12 months, were identified by systematic review. Intracoronary BMSC therapy resulted in an overall significant improvement in left ventricular ejection fraction (LVEF) by 2.74 % (95 % confidence interval (CI) 2.09-3.39, P < 0.00001, I(2) = 84 %) at 3-6-month follow-up and 5.1 % (95 % CI 4.16-6.03, P < 0.00001 and I(2) = 85 %) at 12 months. The left ventricular end-systolic volume (LVESV) and wall motion score index (WMSI) were also reduced at 3-6 months. At 12 months, left ventricular end-diastolic volume (LVEDV), LVESV, and WMSI were significantly reduced in BMSC group. In conclusion, intracoronary BMSC therapy at post-STEMI is safe and effective in patient with acute STEMI.

Short‐ and long‐term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST‐segment elevation myocardial infarction: a meta‐analysis of randomized control trials

Bone marrow stem cell (BMSC) treatment of ST-segment elevation myocardial infarction (STEMI) has been primarily via the intracoronary route or via endogenous mobilization using granulocyte colony-stimulating factor (G-CSF). Studies have provided conflicting results. We therefore performed a meta-analysis of these treatments, examining short- and long-term efficacy and safety. Randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered within 9 days of reperfusion, were identified by systematic search. Random effects models were used to calculate pooled effects of clinical outcomes, with meta-regression to assess dependence of the magnitude of effect sizes on study characteristics. Twenty-nine RCTs enrolling 1830 patients were included. Intracoronary BMSC therapy resulted in an overall improvement in left ventricular ejection fraction (LVEF) of 2.70% [95% confidence interval (CI) 1.48-3.92; P < 0.001] in the short term and 3.31% (95% CI 1.87-4.75; P < 0.001) longer term. Meta-regression suggested a dose-response relationship between quantity of CD34(+) cells delivered and increase in LVEF (P = 0.007). G-CSF treatment resulted in a trend towards similar benefits (P = 0.20). No significant differences were observed in pooled adverse outcome rates between intervention and control groups of either treatment approach, except for lower revascularization rates with intracoronary BMSC vs. control (odds ratio 0.68, 95% CI 0.47-0.97; P = 0.03). Intracoronary BMSC therapy post-STEMI improves LVEF beyond standard medical treatment, in both the short and longer term. G-CSF treatment shows positive but non-significant trends. Both treatments demonstrate safety comparable with conventional medical treatment.

Advances in Cardiology: Clinical Trial Update

Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed.

Evolución a largo plazo de la función ventricular tras la terapia celular intracoronaria en el infarto agudo de miocardio

Controversy surrounds the long-term effects of intracoronary bone marrow stem cell transplantation after ST-elevation acute myocardial infarction (STEAMI). We report on the long-term changes in left ventricular function observed in 29 patients with STEAMI who were treated using this technique. Cardiac magnetic resonance imaging was performed at baseline, 6 months after transplantation, and long-term follow-up (median 27 months, interquartile range 24–35 months). The left ventricular ejection fraction had improved significantly by 6 months (from 47.6 ± 8.9% to 52.7 ± 11.6%; P = .001) and this improvement was maintained long-term, at 52.4 ± 11.8% ( P = .01 vs. baseline and P = .999 vs. 6 months). There was no significant change from baseline in end-diastolic or end-systolic ventricular volume. Our findings indicate the improvement in injection fraction occurs soon after stem cell transplantation, within the first 6 months, and remains unchanged at long-term follow-up. Full English text available from: www.revespcardiol.org

Long-Term Changes in Left Ventricular Function Following Intracoronary Stem Cell Transplantation for Acute Myocardial Infarction

Controversy surrounds the long-term effects of intracoronary bone marrow stem cell transplantation after ST-elevation acute myocardial infarction (STEAMI). We report on the long-term changes in left ventricular function observed in 29 patients with STEAMI who were treated using this technique. Cardiac magnetic resonance imaging was performed at baseline, 6 months after transplantation, and long-term follow-up (median 27 months, interquartile range 24–35 months). The left ventricular ejection fraction had improved significantly by 6 months (from 47.6 ± 8.9% to 52.7 ± 11.6%; P = .001) and this improvement was maintained long-term, at 52.4 ± 11.8% ( P = .01 vs. baseline and P = .999 vs. 6 months). There was no significant change from baseline in end-diastolic or end-systolic ventricular volume. Our findings indicate the improvement in injection fraction occurs soon after stem cell transplantation, within the first 6 months, and remains unchanged at long-term follow-up.

Effects of intracoronary injection of autologous bone marrow-derived stem cells on natriuretic peptides and inflammatory markers in patients with acute ST-elevation myocardial infarction

Intracoronary administration of autologous bone marrow stem cells (BMC) has been shown to result in a subtle improvement of global left ventricular ejection fraction after ST-elevation myocardial infarction (STEMI), but the overall benefits of BMC therapy are still unclear. We studied the influence of intracoronary injections of BMC on levels of natriuretic peptides and inflammatory mediators, which are well established prognostic biomarkers, in patients with STEMI. In this randomized, double-blind study, consecutive patients with an acute STEMI treated with thrombolysis followed by PCI 2-6 days after STEMI, were randomly assigned to receive either intracoronary BMC or placebo medium into the infarct-related artery. Blood samples were drawn for biochemical determinations. From baseline to 6 months, there was a significant decrease in the levels of N-terminal probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) in the whole patient population (P < 0.001 for all). However, no difference was observed between the BMC group (n = 39) and the placebo group (n = 39) in the change of the levels of NT-proANP (median -54 vs. +112 pmol/L), NT-proBNP (-88 vs. -115 pmol/L) or inflammatory markers IL-6 (-3.86 vs. -5.61 pg/mL), hsCRP (-20.29 vs. -22.36 mg/L) and tumor necrosis factor α (-0.12 vs. -0.80 pg/mL) between baseline and 6 months. Intracoronary BMC therapy does not appear to exert any significant effects on the secretion of natriuretic peptides or inflammatory biomarkers in STEMI patients.

Cell distribution after intracoronary bone marrow stem cell delivery in damaged and undamaged myocardium: implications for clinical trials

IntroductionEarly randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion.MethodsMyocardial infarction was induced using balloon inflation in the left coronary artery in domestic pigs. At seven days post-myocardial infarction, 1 × 10(8) autologous bone marrow mononuclear cells were labeled with fluorescent marker and/or 99mTc radiotracer, and delivered using intracoronary or peripheral intravenous injection (leg vein).ResultsScintigraphic analyses and Υ-emission radioactivity counting of harvested organs showed a significant cell fraction retained within the heart after intracoronary injection (6 ± 1.7% of injected radioactivity at 24 hours), whereas following peripheral intravenous cell injection, no cardiac homing was observed at 24 hours and cells were mainly detected within the lungs. Importantly, no difference was observed in the percentage of retained cells within the myocardium in the presence or absence of myocardial infarction. Histological evaluation did not show arterial occlusion in both animal groups and confirmed the presence of bone marrow mononuclear cells within the injected myocardium area.ConclusionsIntravenous bone marrow mononuclear cell injection was ineffective to target myocardium. Myocardial cell distribution following intracoronary injection did not depend on myocardial infarction presence, a factor that could be useful for cardiac cell therapy in patients with chronic heart failure of non-ischemic origin or with ischemic myocardium without myocardial infarction.

First 5 years' follow-up of first group of South American patients with repaired myocardial infarction by autologous intracoronary bone marrow stem cells implant

First 5 years' follow-up of first group of South American patients with repaired myocardial infarction by autologous intracoronary bone marrow stem cells implant

Impact of Timing on Efficacy and Safetyof Intracoronary Autologous Bone Marrow Stem Cells Transplantation in Acute Myocardial Infarction: A Pooled Subgroup Analysis of Randomized Controlled Trials

Until now there were no clinical studies or systematic reviews to investigate the impact of timing on efficacy and safety of intracoronary bone marrow stem cell (BMSC) transfer in patients with acute myocardial infarction (AMI). Timing of BMSC administration might play an important role in the therapeutic response in AMI patients. A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine (EBM) databases was made on randomized controlled trials with at least 3-month follow-up data for patients with AMI undergoing emergent percutaneous coronary intervention (PCI) and receiving intracoronary BMSC transfer thereafter. A total of 7 trials with 660 patients were available for analysis. Compared to baseline level, BMSC transfer at 4 to 7 days post-AMI significantly improved left ventricular ejection fraction (LVEF; 4.63% increase, 95% confidence interval [CI]: 1.00%-8.26%, P = 0.01), reduced left ventricular (LV) end-systolic dimensions (95% CI: - 0.53 - 0.02, P = 0.03), decreased the incidences of revascularization (odds ratio [OR]: 0.60, 95% CI: 0.37-0.97, P = 0.04), decreased the cumulative clinical events of death or recurrent myocardial infarction (OR: 0.32, 95% CI: 0.11-0.95, P = 0.04), and decreased culprit artery restenosis or ventricular arrhythmia (OR: 0.59, 95% CI: 0.36-0.96, P = 0.03) however these improvements did not reach statistical significance in emergent transfer trials (within 24 hour post-AMI). Compared with emergent transfer, intracoronary BMSC therapy at 4 to 7 days also significantly reduced the incidence of revascularization (P for interaction = 0.02). BMSC transfer at 4 to 7 days post-AMI was superior to that within 24 hours in improving LVEF, decreasing LV end-systolic dimensions, and reducing the incidence of revascularization.

Stem Cells Improve Left Ventricular Function in Acute Myocardial Infarction

Animal studies have suggested dramatic improvement in cardiac function after acute myocardial infarction (AMI) through regeneration of the myocardium or neovascularization by transfer of cells derived from bone marrow (BMC) generated clinical studies. Recently published small sized studies have yielded mixed results, leaving the question unanswered. We analyzed data from these studies in a meta-analysis to investigate if intracoronary stem cell therapy was effective in improving cardiac function. A total of 7 randomized controlled trials meeting the inclusion criteria were identified by a systematic literature search. Primary endpoint was change in global left ventricular ejection fraction (LVEF) baseline to follow-up (ranging between 3 to 6 months). The meta-analysis consisted of 516 patients (BMC group, 256; control group, 260). A 2-sided alpha error of less than .05 was considered to be statistically significant (P<.05). There were no significant differences in patient characteristics between the BMC treatment and control groups at baseline. Compared to the control group, patients in the BMC treatment group had significantly greater increase in LVEF from baseline to follow-up (mean difference: 6.108%; SE: 1.753%; 95% confidence interval [CI]: 2.672%- 9.543%; P<.001). The present meta-analysis suggests that intracoronary bone marrow stem cell infusion may be effective in improving left ventricular systolic function in patients after acute myocardial infarction.

Intracoronary autologous bone marrow stem cells transfer for patients with acute myocardial infarction: A meta-analysis of randomised controlled trials

Background Conflicting results existed now on the clinical utility of intracoronary bone marrow stem cells (BMSC) transfer for acute myocardial infarction (AMI). This study sought to analyze the efficacy and safety of autologous BMSC transfer in patients with AMI by performing a meta-analysis based on published randomised controlled trials. Methods A systematic literature search of PubMed, MEDLINE, BIOSIS, EMBASE, and Cochrane EBM databases during the period of 1990–2007 was made, objective being the randomised controlled trials in patients with AMI who underwent primary percutaneous coronary intervention (PCI) and received intracoronary BMSC transfer, and were followed up for at least 3 months. Results A total of 6 trials with 525 patients were available for analysis. The pooled statistics showed the mean increase in left ventricular ejection fraction (LVEF) from baseline was 7.05% in BMSC group ( p = 0.01), whereas only 2.46% in control group ( p = 0.02), and the effect on the absolute change in LVEF was an increase of 4.77% compared with the control (95% confidence interval [CI] 1.42% to 8.12%; p = 0.005). The similar effect on left ventricular (LV) end-diastolic dimensions was demonstrated in inter-group comparison (standardized mean difference [SMD] = − 0.15, 95%CI − 0.50 to 0.20; p = 0.41). The incidence of major adverse cardiac events was also similar in two groups but in favor of BMSC group (relative risk [RR] = 0.85, 95%CI, 0.61 to 1.19; p = 0.34). Conclusions Post PCI BMSC transplantation in patients with AMI significantly increases LVEF but has no effects on LV remodeling, and there is not an incremental effect on the occurrence of major adverse cardiac events in the observed period.

Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure☆ The Danish Stem Cell study—Congestive Heart Failure trial (DanCell‐CHF)

It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects. To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. The study was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. 32 patients were included. LV ejection fraction remained unchanged (33+/-9% vs. 34+/-10% after 8 months, p=0.30). Likewise, there was no significant change in LV end-systolic volume, wall motion score index (WMSI) or contractile reserve. At 12 months, a decrease in target vessel WMSI was seen (2.17+/-0.34 vs. 2.06+/-0.46, p=0.02). Furthermore, NYHA class improved (p<0.0001). No deaths were observed. In this non-randomised study, no change in LV ejection fraction could be demonstrated after repeated intracoronary bone marrow stem cell treatment in patients with chronic ischaemic heart failure.