Intracoronary Autologous Bone Marrow Cell Research Articles

Adenosine stress perfusion cardiac magnetic resonance imaging in patients undergoing intracoronary bone marrow cell transfer after ST-elevation myocardial infarction: the BOOST-2 perfusion substudy.

In the placebo-controlled, double-blind BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) 2 trial, intracoronary autologous bone marrow cell (BMC) transfer did not improve recovery of left ventricular ejection fraction (LVEF) at 6months in patients with ST-elevation myocardial infarction (STEMI) and moderately reduced LVEF. Regional myocardial perfusion as determined by adenosine stress perfusion cardiac magnetic resonance imaging (S-CMR) may be more sensitive than global LVEF in detecting BMC treatment effects. Here, we sought to evaluate (i) the changes of myocardial perfusion in the infarct area over time (ii) the effects of BMC therapy on infarct perfusion, and (iii) the relation of infarct perfusion to LVEF recovery at 6months. In 51 patients from BOOST-2 (placebo, n = 10; BMC, n = 41), S-CMR was performed 5.1 ± 2.9days after PCI (before placebo/BMC treatment) and after 6months. Infarct perfusion improved from baseline to 6months in the overall patient cohort as reflected by the semi-quantitative parameters, perfusion defect-infarct size ratio (change from 0.54 ± 0.20 to 0.43 ± 0.22; P = 0.006) and perfusion defect-upslope ratio (0.54 ± 0.23to0.68 ± 0.22; P < 0.001), irrespective of randomised treatment. Perfusion defect-upslope ratio at baseline correlated with LVEF recovery (r = 0.62; P < 0.001) after 6months, with a threshold of 0.54 providing the best sensitivity (79%) and specificity (74%) (area under the curve, 0.79; 95% confidence interval, 0.67-0.92). Infarct perfusion improves from baseline to 6months and predicts LVEF recovery in STEMI patients undergoing early PCI. Intracoronary BMC therapy did not enhance infarct perfusion in the BOOST-2 trial.

Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST-2 randomised placebo-controlled clinical trial.

Intracoronary infusion of autologous nucleated bone marrow cells (BMCs) enhanced the recovery of left ventricular ejection fraction (LVEF) after ST-segment elevation myocardial infarction (STEMI) in the randomised-controlled, open-label BOOST trial. We reassessed the therapeutic potential of nucleated BMCs in the randomised placebo-controlled, double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway. Using a multiple arm design, we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy. Between 9 March 2006 and 16 July 2013, 153 patients with large STEMI were randomly assigned to receive a single intracoronary infusion of placebo (control group), high-dose (hi)BMCs, low-dose (lo)BMCs, irradiated hiBMCs, or irradiated loBMCs 8.1 ± 2.6 days after percutaneous coronary intervention (PCI) in addition to guideline-recommended medical treatment. Change in LVEF from baseline (before cell infusion) to 6 months as determined by MRI was the primary endpoint. The trial is registered at Current Controlled Trials (ISRCTN17457407). Baseline LVEF was 45.0 ± 8.5% in the overall population. At 6 months, LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hiBMC group. The estimated treatment effect was 1.0 percentage points (95% confidence interval, -2.6 to 4.7; P = 0.57). The treatment effect of loBMCs was 0.5 percentage points (-3.0 to 4.1; P = 0.76). Likewise, irradiated BMCs did not have significant treatment effects. BMC transfer was safe and not associated with adverse clinical events. The BOOST-2 trial does not support the use of nucleated BMCs in patients with STEMI and moderately reduced LVEF treated according to current standards of early PCI and drug therapy.

Multicentre, randomized, double-blind trial of intracoronary autologous mononuclear bone marrow cell injection in non-ischaemic dilated cardiomyopathy (the dilated cardiomyopathy arm of the MiHeart study).

Pre-clinical and few clinical studies suggest that transplantation of autologous bone marrow mononuclear cells (BMNC) improves heart function in dilated cardiomyopathies. Our objective was to determine if intracoronary injection of autologous BMNC improves the left ventricular ejection fraction (LVEF) of patients with non-ischaemic dilated cardiomyopathy (NIDCM). This study was a multicentre, randomized, double-blind, placebo controlled trial with a follow-up of 12 months. Patients with NIDCM and LVEF <35% were recruited at heart failure ambulatories in specialized hospitals around Brazil. One hundred and sixty subjects were randomized to intracoronary injection of BMNC or placebo (1:1). The primary endpoint was the difference in change of LVEF between BMNC and placebo groups as determined by echocardiography. One hundred and fifteen patients completed the study. Left ventricular ejection fraction decreased from 24.0% (21.6-26.3) to 19.9% (15.4-24.4) in the BMNC group and from 24.3% (22.1-26.5) to 22.1% (17.4-26.8) in the placebo group. There were no significant differences in changes between cell and placebo groups for left ventricular systolic and diastolic volumes and ejection fraction. Mortality rate was 20.37% in placebo and 21.31% in BMNC. Intracoronary injection of autologous BMNC does not improve left ventricular function in patients with NIDCM. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00333827.

Mesenchymal stem cells and cardiac regeneration: a sophisticated approach depends on trophic effects—what's left over? Focus on “Activation of Toll-like receptor 3 amplifies mesenchymal stem cell trophic factors and enhances therapeutic potency”

application of stem cells for tissue, in particular cardiac, regeneration represents a promising field of investigation but has not achieved clinical utility ([Fig. 1][1]). From the latter point of view, Strauer and colleagues ([7][2]) in 2001 achieved an important milestone by their administration

Intracoronary bone marrow cell application for terminal heart failure in children

In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports. Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction. Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.

Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial

Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed. Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.

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.

Cell treatment after acute myocardial infarction prevents early decline in circulating IGF-1

Objectives. To examine the influence of intracoronary autologous bone marrow cell transplantation after acute myocardial infarction on circulating growth factors and their relationship to left ventricular function. Methods. Circulating insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), stromal derived factor-1-alpha (SDF-1α), and transforming growth factor beta (TGF-β) were measured in patients randomized to cell treatment or control, in the ASTAMI study. Autologous cells were injected intracoronary on day 6; blood was sampled on days 5, 9, and at three months. Left ventricular ejection fraction was recorded by electrocardiogram-gated single photon emission computed tomography at six months. Results. Only change in IGF-1 from baseline to three months differed between groups (p=0.024). A weak but significant correlation was found between left ventricular ejection fraction and the averaged IGF-1 concentrations of all patients (r=0.24, p=0.02). Patients with IGF-1 above or below median (102 ng/ml) had a left ventricular ejection fraction of 52.3% (±11.4) versus 46.4% (±12.2) respectively (p=0.017). Conclusions. Intracoronary bone marrow cell treatment after myocardial infarction attenuates a reduction in circulating IGF-1. IGF-1 levels over time were weakly, but significantly correlated to left ventricular ejection fraction.

Long-term effects of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: 5-year results from the randomized-controlled BOOST trial--an echocardiographic study

We have recently observed that intracoronary autologous bone marrow cell (BMC)-transfer improves parameters of diastolic function in patients after acute myocardial infarction at 6 and 18 months. There is no clinical study addressing the long-term effect of BMC transfer on diastolic function. Therefore, we conducted a 5-year follow-up of the BOOST trial to evaluate a sustained benefit on echocardiographic parameters on diastolic function. After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation MI, patients were randomized to a control (n = 28) or BMC transfer group (n = 28). Echocardiography was performed at 4.5 +/- 1.5 days after PCI, at 6, 18, and 60 months. Diastolic function was determined by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (E(a)/A(a) ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall treatment effect of BMC transfer on E/A (0.25 +/- 0.10; 95% CI 0.05-0.44; P = 0.01). E/A ratio was significantly lower at 6 (Control 0.90 +/- 0.07; BMC 1.23 +/- 0.14; P = 0.03) and 18 months (Control 0.87+/-0.04; BMC 1.13 +/- 0.09; P = 0.01) in the control group, whereas E/A ratio was not different at 60 months between both groups (Control 0.90 +/- 0.06; BMC 1.05 +/- 0.07; P = 0.12). We found no overall effect of BMC transfer on E(a)/A(a) ratio (0.21 +/- 0.14; 95% CI -0.03 to 0.46; P = 0.09), DT (-12 +/- 11 ms; 95% CI -21 to 28; P = 0.75), IVRT -6 +/- 7 ms; 95% CI -9 to 19; P = 0.43), and E/E(a) ratio (0.58 +/- 0.88; 95% CI -1.18 to 2.34; P = 0.51). Intracoronary autologous BMC transfer provides an overall treatment effect on echocardiographic parameters of diastolic function in patients after AMI. However, this effect is basically related to an early improvement of parameters of diastolic function without a sustained effect on long-term follow-up.

The BALANCE Study: Clinical Benefit and Long-Term Outcome After Intracoronary Autologous Bone Marrow Cell Transplantation in Patients With Acute Myocardial Infarction

The aim of this study was to investigate the quantitative amount of improvement of ventricular hemodynamic status, geometry, and contractility as well as the long-term clinical outcome of cell-treated patients after acute myocardial infarction (AMI).Animal experiments as well as clinical studies have demonstrated that autologous bone marrow cell (BMC) transplantation might improve ventricular function and prevent remodeling.Sixty-two patients underwent intracoronary autologous BMC transplantation 7 +/- 2 days after AMI. Cells were infused directly into the infarct-related artery. The control group consisted of 62 patients with comparable left ventricular (LV) ejection fraction (EF) and diagnosis. All patients had several examinations (e.g., coronary angiography, right heart catheterization, biplane left ventriculography, electrocardiogram [ECG] at rest and exercise, echocardiography, late potential [LP], heart rate variability [HRV], and 24-h Holter ECG). The therapeutic follow-up was performed 3, 12, and 60 months after BMC therapy.Three months after BMC therapy there was significant improvement of EF and stroke volume index. The infarct size was significantly reduced by 8%. Contraction velocities (lengths/second, volumes/second) increased significantly and the slope of the ventricular function curve (systolic pressure/end-systolic volume) became steeper. There was significant improvement of contractility in the infarct zone, as evidenced by a 31% increase of LV velocity of shortening (VCF), preferably in the border zone of the infarct zone. In contrast, the noninfarcted area showed no difference in VCF before and after BMC therapy. Furthermore, decreases of abnormal HRV, LP, and ectopic beats were documented after BMC therapy. Twelve and 60 months after BMC therapy the parameters of contractility, hemodynamic status, and geometry of the LV were stable. The exercise capacity of treated patients was significantly augmented, and the mortality was significantly reduced in comparison with the control group.BMC therapy leads to significant and longstanding improvements of LV performance as well as quality of life and mortality of patients after AMI. After BMC therapy, no side effects were observed, showing that BMC therapy is safe.

Effect of Persistent Microvascular Obstruction on Post-infarction Ventricular Remodeling Following Intracoronary Bone-Marrow Cell Transplantation: A Contrast-Enhanced Cardiac Magnetic Resonance Study

Late contrast-enhanced cardiac magnetic resonance (CMR) enables areas of persistent microvascular obstruction (PMO) to be detected early after acute myocardial infarction. Our aim was to evaluate the impact of PMO on subsequent ventricular remodeling in a cohort of patients with acute ST-elevation myocardial infarction (STEMI) who underwent intracoronary autologous bone-marrow mononuclear cell (ABMMC) transplantation. In total, 14 patients underwent intracoronary transplantation of 66+/-39 x 10(6) ABMMCs 8+/-2 days following successful revascularization of a STEMI (i.e., TIMI flow grade 3 in the affected artery). Serial CMR studies with gadolinium-DTPA enhancement were performed at baseline and 10 months after infarction. Left ventricular volume and ejection fraction, regional contractility and the infarct size were measured and the presence of PMO (defined as hypoenhanced areas within the infarcted zone) was investigated. Overall, PMO was detected in five of the 14 patients (36%). Those with PMO tended to have a larger infarct size, larger ventricular volumes, and poorer regional and global left ventricular systolic function in baseline studies than those without PMO. At follow-up, there were significant associations between PMO and an increase in end-diastolic volume (25+/-24 mL vs. -2+/-19 mL; P=.037), the absence of an increase in end-diastolic parietal thickness (P=.027), and a smaller reduction in the number of akinetic or dyskinetic segments. The detection of PMO by CMR early after successful revascularization of a STEMI in patients who underwent intracoronary ABMMC transplantation was associated with adverse left ventricular remodeling.

Abstract 3400: Regeneration of Human Infarcted Heart Muscle in Chronic Coronary Artery Disease after myocardial infarction: Controlled study with Intracoronary Autologous Mononuclear Bone Marrow Cell Transplantation (IACT-Study)

Introduction: Remodeling of the left ventricle (LV) after myocardial infarction (MI) represents a major cause of infarct-related heart failure and death. After acute myocardial infarction transplantation of bone marrow cells (BMCs) leads to regeneration of infarcted zones due to neovascularization and regeneration of myocardium. We investigated cardiac performance of intracoronary transplantation of autologous BMCs in patients with chronic ischemic heart disease, suffered from transmural myocardial infarction. Methods: We treated 120 consecutive patients (51±14 years) with chronic myocardial infarction by intracoronary transplantation of autologous bone marrow mononuclear cells (BMCs) and compared them with a consecutive enrolled representative control group (n=45, 53±11 years). Bone marrow was harvested from the hip (~80 ml) and mononuclear cells were identified including CD34+, AC133+ and CD 34−, CD45−, CD14− cells. The median number of mononuclear cells harvested after overnight culture was 104 x 10 6 Results: After 3 months in the transplantation group, infarct size was reduced from (32±9 to 25±9%) significantly (p&lt;0.001), and global left ventricular ejection fraction (45±9 to 51±10%) significantly (p&lt;0.001); as well as infarction wall movement velocity (1.86 ± 0.72 to 3,12 ± 0.78cm/s) significantly (p&lt;0.001), while in the control group no significant changes were observed during 3 months follow-up in infarct size (29±9 to 28±9%), in left ventricular ejection fraction (48±10 to 50±15%) and in wall movement velocity of infarcted area (1.81 ± 0.76 to 1.92 ± 0.78cm/s). After bone marrow cell transplantation, there was an significantly (p&lt;0.05) improvement of maximum oxygen uptake (VO2max, +12%) and significantly (p&lt;0.05) of regional 18F-Fluor-Desoxy-Glucose (FDG) uptake (PET) into infarcted tissue (+15%). Conclusions: These results demonstrate that selective intracoronary transplantation of autologous BMCs may reduce infarct size and improve LV function and myocardial glucose uptake in chronic ischemic heart disease after chronic infarcted myocardium.

451 Influence of regeneration of heart muscle by intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction on Mobilization of CD34+ and CD133+ circulating progenitor cells

451 Influence of regeneration of heart muscle by intracoronary autologous bone marrow cell transplantation in patients with acute myocardial infarction on Mobilization of CD34+ and CD133+ circulating progenitor cells

Circulating Endothelial Progenitor Cells Characterization, Function and Relationship with Cardiovascular Risk Factors

Since the first description of putative progenitor endothelial cells mobilized from bone marrow by stimuli like ischemia and cytokines, several studies in animals have confirmed their role in neovascularization of ischemic organs. In ischemic myocardium endothelial progenitor cells can prevent cardiomyocyte apoptosis, reduce remodeling and improve cardiac function. These observations led to the hypothesis of endothelial progenitor cells as possible cell-based therapy in patients by autologous transplantation in ischemic tissue or by improving peripheral circulating numbers with mobilization by cytokines. Early trials, including a randomized one, suggest that the intracoronary autologous bone marrow cell transfer after myocardial infarction exerts at least short term functional benefits. Since endothelial damage and dysfunction play a critical role in atherosclerosis disease, research interest was addressed to evaluate the role of progenitor endothelial cells in vascular endothelial layer maintenance. Opposing to local resident endothelial cells poor proliferation rate, progenitor endothelial cells regenerative capacity, homing and integration into blood vessels have been interpreted as a protective role of these cells in vascular homeostasis. Indeed, the number and function of endothelial progenitor cells relate with the progression of atherosclerosis; the accumulation of cardiovascular risk factors or an increased overall risk are inversely associated with endothelial progenitor cells number and function. Finally, recent studies have shown a role of progenitor cells numbers to predict cardiovascular events, raising endothelial progenitor cells to the podium of novel prognostic biomarker.

750 Influence of regeneration of heart muscle by intracoronary autologous bone marrow cell transplantation in patients with chronic ischemic heart disease on the mobilization of CD34+ and CD133+ circulating progenitor cells

750 Influence of regeneration of heart muscle by intracoronary autologous bone marrow cell transplantation in patients with chronic ischemic heart disease on the mobilization of CD34+ and CD133+ circulating progenitor cells

Electrical Coupling of Cardiac Myocyte Cell Sheets to the Heart

See related article, pages 705–712 The past 20 years have seen tremendous progress in the medical treatment of cardiac diseases, a progress that actually translated into decreased cardiovascular morbidity and mortality in clinical practice.1 Yet evidence accumulates that interventions intended to slow down the progression of chronic heart diseases have approached their limit. This may be one of the reasons why the recent progress in stem cell biology has stirred so much attention. In addition, recent studies suggesting the existence of cell populations in the adult organism that, albeit at a low rate and insufficiently, endogenously replace cardiac myocytes and endothelial and smooth muscle cells have challenged the dogma of the heart as a nonregenerating organ.2–5 Such cell populations could be accessed in biopsies and principally serve as a source to replace cardiac myocytes and other cardiac cell types lost after myocardial infarction or other pathologies. Human embryonic stem cell lines, on the other hand, can nowadays be generated from human blastocysts (accessible from IVF leftovers6) at a high success rate and have been unambiguously shown to generate human cardiac myocytes.7–9 Thus, despite many open questions and some controversy in the field (reviews in references 10,11), cardiac regenerative therapy has become a realistic perspective. But what to do with stem cells or their derivatives, given that means will be provided to generate them at sufficient numbers? The most straightforward strategy is to infuse or inject these cells into the injured heart and to develop methods to increase the fraction of cells that home and survive in the heart and differentiate to the desired functional elements. This strategy has already been clinically evaluated, but gave mixed results,12–16 potentially also because the homing rate after infusion and the survival rate after intramyocardial injections are very low. …

Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial

We have recently shown in the randomized-controlled BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial that intracoronary autologous bone marrow cell (BMC) transfer improves left ventricular (LV) ejection fraction recovery in patients after acute myocardial infarction (AMI). However, the impact of BMC therapy on LV diastolic function in patients after AMI has remained uncertain. Using (tissue) Doppler echocardiography, we evaluated the effects of BMC transfer on LV diastolic function in patients enrolled in the BOOST trial. After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (MI), patients were randomized to a control (n = 29) or BMC transfer group (n = 30). Diastolic function was determined 4.5+/-1.5 days after PCI, at 6 months, and at 18 months by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall effect of BMC transfer on E/A [0.33+/-0.12; 95% confidence interval (CI): 0.09-0.57; P = 0.008] and Ea/Aa ratios (0.29+/-0.14; 95% CI: 0.01-0.57; P = 0.04). In contrast, we found no effect of BMC transfer on DT (-5+/-14 ms; 95% CI: -33 to 22; P = 0.70), IVRT (-7+/-7 ms; 95% CI: -20 to 6; P = 0.29), and E/Ea ratio (0.35+/-0.14; 95% CI: -0.92 to 1.62; P = 0.57). Intracoronary autologous BMC transfer improves echocardiographic parameters of diastolic function in patients after AMI.

Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease: The IACT Study

Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease: The IACT Study

Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease: The IACT Study

Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease: The IACT Study

Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease: The IACT Study

Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. After acute MI, bone marrow-derived cells improve cardiac function. We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation.