***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background Studies of the transplantation of autologous bone marrow cells ( BMC s ) in patients with chronic ischemic heart disease have assessed effects on viable , peri-infa rct tissue . We conducted a single-blinded , r and omized , controlled study to investigate whether intramuscular or intracoronary administration of BMC s into nonviable scarred myocardium during CABG improves contractile function of scar segments compared with CABG alone . Methods Elective CABG patients ( n = 63 ) , with established myocardial scars diagnosed as akinetic or dyskinetic segments by dobutamine stress echocardiography and confirmed at surgery , were r and omly assigned CABG alone ( control ) or CABG with intramuscular or intracoronary administration of BMC s. The BMC s , which were obtained at the time of surgery , were injected into the mid-depth of the scar in the intramuscular group or via the graft conduit supplying the scar in the intracoronary group . Contractile function was assessed in scar segments by dobutamine stress echocardiography before and 6 months after treatment . Results The proportion of patients showing improved wall motion in at least one scar segment after BMC treatment was not different to that observed in the control group ( P = 0.092 ) . Quantitatively , systolic fractional thickening in scar segments did not improve with BMC administration . Furthermore , BMC s did not improve scar transmurality , infa rct volume , left ventricular volume , or ejection fraction . Conclusion Injection of autologous BMC s directly into the scar or into the artery supplying the scar is safe but does not improve contractility of nonviable scarred myocardium , reduce scar size , or improve left ventricular function more than CABG alone AIMS Intracoronary administration of autologous bone marrow cells ( BMC s ) leads to a modest improvement in cardiac function , but the effect on myocardial viability is unknown . The aim of this r and omized 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 infa rct ion ( AMI ) and to identify predictive factors for improvement of myocardial viability . METHODS AND RESULTS One hundred and one patients with AMI and successful reperfusion , LVEF ≤45 % , and decreased myocardial viability ( resting Tl201-SPECT ) were r and omized 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 . CONCLUSION 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 . CLINICAL TRIAL REGISTRATION INFORMATION URL : http://www . clinical trials.gov . Unique identifier NCT00200707 Aims To evaluate the safety profile and efficacy of bone marrow mononuclear cells ( BMMNC ) transplantation for ST-segment elevation myocardial infa rct ion ( STEMI ) by assessing patients and their left ventricular function at up to 4 years follow-up . Methods and results Eighty-six patients with STEMI who had successfully undergone percutaneous coronary intervention ( PCI ) were r and omized to receive intracoronary injection of BMMNC ( n = 41 ) or saline ( n = 45 ) . Left ventricular ejection fraction , as evaluated by UCG , was markedly improved at 6 months ( 0.484 ± 0.5 vs. 0.457 ± 0.6 , P = 0.001 ) , 1 year ( 0.482 ± 0.7 vs. 0.446 ± 0.6 , P < 0.001 ) , and 4 years ( 0.505 ± 0.8 vs. 0.464 ± 0.8 , P < 0.001 ) after BMMNC transplant when compared with control group . However , the current cell therapy did not improve the myocardial viability of the infa rct ed area as assessed by single-photon emission computed tomography analysis at 4 years post-transplant ( 0.263 ± 0.007 in BMMNC group vs. 0.281 ± 0.008 in control group , P = 0.10 ) . During the follow-up period , one control group case ( 2.2 % ) of in-stent restenosis was confirmed by coronary angiography and underwent repeat PCI . Also during follow-up , one death ( 2.2 % ) occurred in the control group , and one patient ( 2.4 % ) in the BMMNC group had transient acute heart failure . Conclusion This study indicates that intracoronary delivery of autologous BMMNC is safe and feasible for STEMI patients who have undergone PCI , and can lead to long-term improvement in myocardial function Background — Intracoronary administration of autologous bone marrow – derived mononuclear cells ( BM-MNC ) may improve remodeling of the left ventricle ( LV ) after acute myocardial infa rct ion . The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospect ively in r and omized clinical trials . Methods and Results — In a multicenter study , we r and omized 200 patients with large , successfully reperfused ST-segment elevation myocardial infa rct ion in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups . In the BM-MNC groups , cells were administered either early ( ie , 5 to 7 days ) or late ( ie , 3 to 4 weeks ) after acute myocardial infa rct ion . Cardiac magnetic resonance imaging was performed at baseline and after 4 months . The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group . The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8 % ( mean±SD ; P=0.74 versus baseline ) in the control group , 1.8±8.4 % ( P=0.12 versus baseline ) in the early group , and 0.8±7.6 % ( P=0.45 versus baseline ) in the late group . The treatment effect of BM-MNC  as estimated by ANCOVA was 1.25 ( 95 % confidence interval , −1.83 to 4.32 ; P=0.42 ) for the early therapy group and 0.55 ( 95 % confidence interval , −2.61 to 3.71 ; P=0.73 ) for the late therapy group . Conclusions — Among patients with ST-segment elevation myocardial infa rct ion and LV dysfunction after successful reperfusion , intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infa rct ion did not improve LV function at 4-month follow-up . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00355186 Background — Intracoronary transfer of autologous bone marrow cells ( BMC s ) may enhance recovery of left ventricular ( LV ) function in patients after acute myocardial infa rct ion ( AMI ) . However , clinical studies addressing the effects of BMC s after AMI have covered only limited time frames ranging from 3 to 6 months . The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered . Methods and Results – After percutaneous coronary intervention with stent implantation ( PCI ) of the infa rct -related artery , 60 patients were r and omized 1:1 to a control group with optimal postinfa rct ion therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8±1.3 days after PCI . Cardiac MRI was performed 3.5±1.5 days , 6±1 months , and 18±6 months after PCI . BMC transfer was not associated with adverse clinical events . In the control group , mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months , respectively . LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points . The difference in LVEF improvement between groups was significant after 6 months but not after 18 months ( P=0.27 ) . The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group ( P=0.001 ) . Conclusions – In this study , a single dose of intracoronary BMC s did not provide long-term benefit on LV systolic function after AMI compared with a r and omized control group ; however , the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy Background —The present sub study of a recently published r and omized trial aim ed to investigate the effect of intramyocardial bone marrow cell injection on diastolic function in patients with chronic myocardial ischemia . Methods and Results —In a total of 50 patients , diastolic function was evaluated before and 3 months after bone marrow cell injection using st and ard echocardiography and strain analysis . In addition , MRI-derived transmitral flow measurements were obtained in a subset of 36 patients . Left ventricular ejection fraction increased from 50±5 % to 54±7 % in the bone marrow cell group , which was a significant improvement as compared with the placebo group ( 52±5 % versus 51±7 % , P=0.001 ) . Filling pressure estimate E/E′ ratio improved from 14±5 at baseline to 12±4 at 3 months in the bone marrow cell group , whereas no improvement was observed in the placebo group ( 13±4 versus 13±5 ) . The improvement in E/E′ ratio was significantly larger in the bone marrow cell group ( P=0.008 ) . Furthermore , the E/A peak flow ratio as assessed by MRI showed a significant increase in the bone marrow cell group as compared with the placebo group ( + 0.16±0.25 versus −0.04±0.21 , P=0.01 ) , which was mainly related to an increase in the early ( E ) peak flow rate in the bone marrow cell group ( from 407±96 mL/s to 468±110 mL/s , P=0.009 as compared with the placebo group ) . Conclusions —The current study demonstrates that intramyocardial bone marrow cell injection is associated with a beneficial effect on myocardial relaxation and filling pressures in patients with chronic myocardial ischemia . Clinical Trial Registration —URL : http://www.trialregister.nl . Unique identifier : NTR400/IS RCT N58194927 OBJECTIVES This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure . BACKGROUND In pre- clinical heart failure models , cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling . METHODS The C-CURE ( Cardiopoietic stem Cell therapy in heart failURE ) trial , a prospect i ve , multicenter , r and omized trial , was conducted in patients with heart failure of ischemic origin who received st and ard of care or st and ard of care plus lineage-specified stem cells .  In the cell therapy arm , bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail . Derived cardiopoietic stem cells , meeting release criteria under Good Manufacturing Practice , were delivered by endomyocardial injections guided by left ventricular electromechanical mapping . Data acquisition and analysis were performed in blinded fashion . The primary endpoint was feasibility/safety at 2-year follow-up . Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy . RESULTS Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75 % and delivery without complications in 100 % of cases . There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy .  Left ventricular ejection fraction was improved by cell therapy ( from 27.5 ± 
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The benefits also persisted when cardiac catheterization was performed in control patients as well .
Although imaging modalities partly influenced the outcomes , LV ejection fraction improved in BMC -treated patients when assessed by magnetic resonance imaging .
Early ( < 48 hours ) BMC injection after myocardial Infa rct ion was more effective in reducing infa rct size , whereas BMC injection between 3 and 10 days proved superior toward improving systolic function .
A minimum of 50 million BMC s seemed to be necessary , with limited additional benefits seen with increasing cell numbers .
BMC therapy was safe and improved clinical outcomes , including all-cause mortality , recurrent myocardial Infa rct ion , ventricular arrhythmia , and cerebrovascular accident during follow-up , albeit with differences between acute myocardial Infa rct ion and chronic ischemic heart disease subgroups .
Transplantation of adult BMC s improves LV ejection fraction , reduces infa rct size , and ameliorates remodeling in  patients with ischemic heart disease .
These effects are upheld in the analyses of studies using magnetic resonance imaging and also after excluding studies with discrepant reporting of outcomes .
BMC transplantation may also reduce the incidence of death , recurrent myocardial Infa rct ion , ventricular arrhythmia , and cerebrovascular accident during follow-up