Intracoronary Infusion Of Bone Marrow Cells Research Articles

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis

The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials. We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes. Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.

Review Article: Current Status of Myocardial Regeneration: New Cell Sources and New Strategies

Clinical trials of stem cell therapy in cardiology are based upon a reasonably solid foundation in animal laboratory research. The most widely used cell source in clinical trials has been the patient's own reconstituted bone marrow cell (BMC) aspirate. Cell sources in human bone marrow include hematopoietic stem cells, mesenchymal progenitor cells, and other cell types with many desirable characteristics. In vitro, they can be induced to become typical sarcomeres with centrally positioned nuclei and abundant mitochondria and to express atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and contractile proteins including myosin heavy chain, myosin light chain, and alpha actin. Intracoronary BMC infusion significantly decreases infarct size, increases myocardial perfusion, and improves regional and global cardiac function. Meta-analyses of clinical trials of intracoronary autologous BMC infusion following acute myocardial infarction (MI) report that the mean absolute increase in ejection fraction (EF) is approximately 3% to 4%. This modest improvement in function appears to persist for 1 year. Some trials have shown that clinical events are reduced at 12 months, but others have reported no long-term clinical benefit, and the only 5-year follow-up suggests persistent benefit with decreased mortality, but also little evidence of significant myocardial regeneration in humans. These results have led to efforts to identify better cell sources and to create more conducive myocardial environment for cell proliferation. Among the cell types are skeletal myoblasts, cardiac stem cells, and induced pluripotent stem cells. Environmental modifiers are designed to increase cell survival, persistence, and proliferation.

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.

Bone marrow for cardiac repair: the importance of characterizing the phenotype and function of injected cells

Administration of adult stem cells for cardiac repair after myocardial infarction (MI) is a revolutionary new strategy that could become clinically feasible in the near term, appears to be safe and relatively cost-effective, and offers tremendous potential to improve prognosis.1 Using diverse cell populations and strategies, several relatively small clinical studies have reported encouraging outcomes, with improvement in various measures of myocardial perfusion and left ventricular (LV) function.2 However, negative data have also emerged, generating controversy regarding the overall efficacy of cell therapy.2 This controversy persists even after the recent publication of the three largest randomized studies to date of cell therapy for cardiac repair.3–5 In the largest of these trials, the multicentre REPAIR-AMI study,3 204 patients received an intracoronary infusion of autologous mononuclear bone marrow cells (BMCs) or placebo (medium) at 3–7 days after a reperfused acute MI. After 4 months, the absolute improvement in global LV ejection fraction (EF) was greater in patients treated with BMCs compared with control patients. After 1 year, BMC treatment was associated with a significant reduction in the combined endpoints of death, recurrent MI, and revascularization and death, recurrent MI, and re-hospitalization for heart failure.3,6 An improvement in LV function and clinical outcome after BMC treatment was also noted in the TOPCARE-CHD trial among patients with an old MI.4 However, no benefit was reported in the other trial of acute MI (the ASTAMI trial),5 in which 100 patients with reperfused acute anterior MI received either intracoronary infusion of BMCs or no intervention at a median of 6 days after MI. After 6 months, there was no difference in LVEF, infarct size, … *Corresponding author. Tel: +1 502 8521837; fax: +1 502 852 6474. E-mail address : rbolli{at}louisville.edu

435 Improvement of regional myocardial function during exercise after cell therapy in chronic ischemic cardiomyopathy

Objectives: We sought to examine changes in regional myocardial deformation during exercise echocardiography, before (pre) and 4 months after (post) intracoronary infusion of autologous bone marrow cells (BMC) in patients with severe chronic ischemic cardiomyopathy (ICM). Background: Longitudinal systolic myocardial strain (s) and strain rate (sr) has proven to be useful for quantifying regional myocardial function during stress echocardiography. Effects of intracoronary infusion of autologous BMC on global and regional myocardial function have not been studied in patients with chronic ICM. Methods: Eight patients with dilated LV and EF< 35% underwent a symptom-limited bicycle exercise echocardiography pre and post BMC infusion. Maximum systolic strain (msys) and peak systolic strain rate (psysr) were measured at rest (r) and exercise (e) pre and post BMC in the mid segment of each akinetic area. Intracoronary infusions of BMC were performed into the artery supplying viable territory detected by exercise echocardiography. Results: Twelve akinetic areas were analysed. Three of the 8 anterior and all of the 4 inferior areas presented viability pre BMC.WMSI did not change at rest and decreased from 1.43 40.17 to 1.38 40.16(p=0.02) at exercise. EF, msys and psysr results at rest and exercise are shown in the table.