***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND We recently demonstrated in a r and omized , double-blind , placebo-controlled trial that intramyocardial bone marrow cell ( BMC ) injection is associated with improvements in myocardial perfusion and anginal symptoms in chronic myocardial ischemia patients . In the present study the results of the crossover phase of this trial , in which patients previously treated with placebo received autologous BMC injections  are reported . This allows a unique intra-patient comparison on the effect of BMC versus placebo injection with elimination of patient-related confounding factors . METHODS In 16 patients ( 14 male , 64 ± 10 years ) , who previously received intramyocardial placebo injections in the setting of a r and omized trial , 100 × 10(6 ) BMC were injected using the NOGA-system . Canadian Cardiovascular Society angina score and quality of life were evaluated at baseline , 3 and 6 months . Tc-99 m single photon emission computed tomography and magnetic resonance imaging were performed at baseline and 3 months to assess myocardial perfusion and left ventricular ( LV ) function . RESULTS Canadian Cardiovascular Society score and quality of life improved significantly after BMC injection as compared to placebo ( P = 0.01 and P = 0.02 , respectively ) . Single photon emission computed tomography revealed a significant greater improvement ( P = 0.03 ) in summed stress score after BMC injection as compared to placebo . LV end-systolic volume significantly decreased after BMC injection but not after placebo injection . LV end-diastolic volume and LV ejection fraction did not change . CONCLUSION Intramyocardial BMC injection in patients with chronic myocardial ischemia who previously received intramyocardial placebo treatment result ed in significant improvement in angina symptoms and myocardial perfusion . These results confirm the outcome of our previously reported r and omized trial Background — Allogeneic mesenchymal precursor cells ( MPCs ) injected during left ventricular assist device ( LVAD ) implantation may contribute to myocardial recovery . This trial explores the safety and efficacy of this strategy . Methods and Results — In this multicenter , double-blind , sham-procedure controlled trial , 30 patients were r and omized ( 2:1 ) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation . The primary safety end point was incidence of infectious myocarditis , myocardial rupture , neoplasm , hypersensitivity reaction , and immune sensitization ( 90 days after r and omization ) . Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support ( 90 days after r and omization ) . Patients were followed up until transplant or 12 months after r and omization , whichever came first . Mean age was 57.4 ( ±13.6 ) years , mean left ventricular ejection fraction was 18.1 % , and 66.7 % were destination therapy LVADs . No safety events were observed . Successful temporary LVAD weaning was achieved in 50 % of MPC and 20 % of control patients at 90 days ( P=0.24 ) ; the posterior probability that MPCs increased the likelihood of successful weaning was 93 % . At 90 days , 3 deaths ( 30 % ) occurred in control patients , and none occurred in MPC patients . Mean left ventricular ejection fraction after successful wean was 24.0 % ( MPC=10 ) and 22.5 % ( control=2 ; P=0.56 ) . At 12 months , 30 % of MPC patients and 40 % of control patients were successfully temporarily weaned from LVAD support ( P=0.69 ) , and 6 deaths ( 30 % ) occurred in MPC patients . Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months . Conclusions — In this preliminary trial , administration of MPCs appeared to be safe , and there was a potential signal of efficacy . Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01442129 Background —This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility . Methods and Results —Twenty-one patients were enrolled in this prospect i ve , nonr and omized , open-label study ( first 14 patients , treatment ; last 7 patients , control ) . Baseline evaluations included complete clinical and laboratory evaluations , exercise stress ( ramp treadmill ) , 2D Doppler echocardiogram , single-photon emission computed tomography perfusion scan , and 24-hour Holter monitoring . Bone marrow mononuclear cells were harvested , isolated , washed , and resuspended in saline for injection by NOGA catheter ( 15 injections of 0.2 cc ) . Electromechanical mapping was used to identify viable myocardium ( unipolar voltage ≥6.9 mV ) for treatment . Treated and control patients underwent 2-month noninvasive follow-up , and treated patients alone underwent a 4-month invasive follow-up according to st and ard protocol s and with the same procedures used as at baseline . Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups ; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up , being relatively higher in control patients . At 2 months , there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups ( P = 0.02 ) on quantitative single-photon emission computed tomography analysis . At 4 months , there was improvement in ejection fraction from a baseline of 20 % to 29 % ( P = 0.003 ) and a reduction in end-systolic volume ( P = 0.03 ) in the treated patients . Electromechanical mapping revealed significant mechanical improvement of the injected segments ( P < 0.0005 ) at 4 months after treatment . Conclusions —Thus , the present study demonstrates the relative safety of intramyocardial injections of bone marrow – derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function 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 Background — SCIPIO is a first-in-human , phase 1 , r and omized , open-label trial of autologous c-kit+ cardiac stem cells ( CSCs ) in patients with heart failure of ischemic etiology undergoing coronary artery bypass grafting ( CABG ) .  In the present study , we report the surgical aspects and interim cardiac magnetic resonance ( CMR ) results . Methods and Results — A total of 33 patients ( 20 CSC-treated and 13 control subjects ) met final eligibility criteria and were enrolled in SCIPIO . CSCs were isolated from the right atrial appendage harvested and processed during surgery . Harvesting did not affect cardiopulmonary bypass , cross-clamp , or surgical times . In CSC-treated patients , CMR showed a marked increase in both LVEF ( from 27.5±1.6 % to 35.1±2.4 % [ P=0.004 , n=8 ] and 41.2±4.5 % [ P=0.013 , n=5 ] at 4 and 12 months after CSC infusion , respectively ) and regional EF in the CSC-infused territory . Infa rct size ( late gadolinium enhancement ) decreased after CSC infusion ( by manual delineation : −6.9±1.5 g [ −22.7 % ] at 4 months [ P=0.002 , n=9 ] and −9.8±3.5 g [ −30.2 % ] at 12 months [ P=0.039 , n=6 ] ) . LV nonviable mass decreased even more ( −11.9±2.5 g [ −49.7 % ] at 4 months [ P=0.001 ] and −14.7±3.9 g [ −58.6 % ] at 12 months [ P=0.013 ] ) , whereas LV viable mass increased ( + 11.6±5.1 g at 4 months after CSC infusion [ P=0.055 ] and + 31.5±11.0 g at 12 months [ P=0.035 ] ) . Conclusions — Isolation of CSCs from cardiac tissue obtained in the operating room is feasible and does not alter practice s during CABG surgery . CMR shows that CSC infusion produces a striking improvement in both global and regional LV function , a reduction in infa rct size , and an increase in viable tissue that persist at least 1 year and are consistent with cardiac regeneration . Clinical Trial Registration — This study is registered with clinical trials.gov , trial number NCT00474461 Intramyocardial bone marrow cell injection has been associated with improvements in myocardial perfusion and left ventricular function . The current sub study of a r and omized , placebo-controlled , double-blinded study , investigated the effect of intramyocardial bone marrow cell injection on myocardial sympathetic innervation in patients with chronic myocardial ischemia . In a total of 16 patients ( 64 ± 8 years , 13 men ) , early and late iodine-123 metaiodobenzylguanidine ( MIBG ) imaging was performed before and 3 months after intramyocardial bone marrow cell injection . No improvements were observed in global early H/M ratio ( P = 0.40 ) , late H/M ratio ( P = 0.43 ) and cardiac washout rate ( P = 0.98 ) . However , late 123-I MIBG SPECT defect score showed a trend to improvement in the bone marrow cell group ( from 31.0 ± 7.1 to 28.1 ± 14.9 ) as compared to the placebo group ( from 33.6 ± 8.5 to 34.5 ± 9.8 , P = 0.055 between groups ) . This trend was mainly driven by a substantial improvement in three bone marrow cell-treated patients , which all had diabetes and severe MIBG defects . In these patients , the extent and severity of MIBG defects improved substantially independent of myocardial perfusion and cell injection sites . The present study does not demonstrate improvements in global cardiac sympathetic nerve innervation after intramyocardial bone marrow cell injection in patients with chronic myocardial ischemia . However , regional analysis of sympathetic nerve innervation reveals improvements in three diabetic patients independent of myocardial perfusion , suggestive of a therapeutic effect on diabetic cardiac sympathetic dysinnervation IMPORTANCE The modest effects of clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells ( BMC s ) in patients with chronic postinfa rct ion heart failure may be attributed to impaired homing of BMC s to the target area . Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue , result ing in enhanced retention of applied BMC s. OBJECTIVE To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMC s improves recovery of left ventricular ejection fraction ( LVEF ) in patients with chronic heart failure . DESIGN , SETTING , AND PARTICIPANTS The CELLWAVE double-blind , r and omized , placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt , Germany , between 2006 and 2011 . INTERVENTIONS Single-blind low-dose ( n = 42 ) , high-dose ( n = 40 ) , or placebo ( n =  
    Output:
    
This systematic review and meta- analysis found low- quality evidence that treatment with bone marrow-derived stem/progenitor cells reduces mortality and improves left ventricular ejection fraction over short- and long-term follow-up and may reduce the incidence of non-fatal myocardial infa rct ion and improve New York Heart Association ( NYHA ) Functional Classification in people with chronic ischaemic heart disease and congestive heart failure .