***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: Aims Cardiopoietic cells , produced through cardiogenic conditioning of patients ’ mesenchymal stem cells , have shown preliminary efficacy . The Congestive Heart Failure Cardiopoietic Regenerative Therapy ( CHART-1 ) trial aim ed to vali date cardiopoiesis-based biotherapy in a larger heart failure cohort . Methods and results This multinational , r and omized , double-blind , sham-controlled study was conducted in 39 hospitals . Patients with symptomatic ischaemic heart failure on guideline -directed therapy ( n = 484 ) were screened ; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion . Those achieving > 24 million mesenchymal stem cells ( n = 315 ) were r and omized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter ( n = 157 ) or sham procedure ( n = 158 ) . Procedures were performed as r and omized in 271 patients ( n = 120 cardiopoietic cells , n = 151 sham ) . The primary efficacy endpoint was a Finkelstein – Schoenfeld hierarchical composite ( all-cause mortality , worsening heart failure , Minnesota Living with Heart Failure Question naire score , 6-min walk distance , left ventricular end-systolic volume , and ejection fraction ) at 39 weeks . The primary outcome was neutral ( Mann – Whitney estimator 0.54 , 95 % confidence interval [ CI ] 0.47–0.61 [ value > 0.5 favours cell treatment ] , P = 0.27 ) . Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200–370 mL ( 60 % of patients ) ( Mann – Whitney estimator 0.61 , 95 % CI 0.52–0.70 , P = 0.015 ) . No difference was observed in serious adverse events . One ( 0.9 % ) cardiopoietic cell patient and 9 ( 5.4 % ) sham patients experienced aborted or sudden cardiac death . Conclusion The primary endpoint was neutral , with safety demonstrated across the cohort . Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted BACKGROUND AIMS Mesenchymal stromal cells ( MSC ) may improve cardiac function following myocardial infa rct ion . MSC can differentiate into cardiomyocytes and endothelial cells while exerting additional paracrine effects . There is limited information regarding the efficacy of route for MSC treatment of severe dilated cardiomyopathy ( DCM ) . The aim of this study was to demonstrate the clinical safety , feasibility and efficacy of direct intramyocardial and intracoronary administration of autologous bone marrow-derived MSC treatment for no-option patients with chronic severe refractory DCM . METHODS Ten symptomatic patients with DCM and refractory cardiac function , despite maximum medical therapy , were selected . Five had ischemic DCM deemed unlikely to benefit from revascularization alone and underwent bypass operations with concurrent intramyocardial MSC injection ( group A ) . Two patients had previous revascularization and three had non-ischemic DCM and received intracoronary MSC injection ( group B ) . RESULTS Group A and B patients received 0.5 - 1.0 × 10(6 ) and 2.0 - 3.0 × 10(6 ) MSC/kg body weight , respectively . All patients remained alive at 1 year . There were significant improvements from baseline to 6 and 12 months in left ventricular ejection fraction and other left ventricular parameters . Scar reduction was noted in six patients by 12 months . CONCLUSIONS Autologous bone marrow MSC treatment is safe and feasible for treating chronic severe refractory DCM effectively , via intracoronary or direct intramyocardial administration at prescribed doses RATIONALE Culture-exp and ed cells originating from cardiac tissue that express the cell surface receptor cKit are undergoing clinical testing as a cell source for heart failure and congenital heart disease . Although accumulating data support that mesenchymal stem cells ( MSCs ) enhance the efficacy of cardiac cKit(+ ) cells ( CSCs ) , the underlying mechanism for this synergistic effect remains incompletely understood . OBJECTIVE To test the hypothesis that MSCs stimulate endogenous CSCs to proliferate , migrate , and differentiate via the SDF1/CXCR4 and stem cell factor/cKit pathways . METHODS AND RESULTS Using genetic lineage-tracing approaches , we show that in the postnatal murine heart , cKit(+ ) cells proliferate , migrate , and form cardiomyocytes , but not endothelial cells . CSCs exhibit marked chemotactic and proliferative responses when cocultured with MSCs but not with cardiac stromal cells . Antagonism of the CXCR4 pathway with AMD3100 ( an SDF1/CXCR4 antagonist ) inhibited MSC-induced CSC chemotaxis but stimulated CSC cardiomyogenesis ( P<0.0001 ) . Furthermore , MSCs enhanced CSC proliferation via the stem cell factor/cKit and SDF1/CXCR4 pathways ( P<0.0001 ) . CONCLUSIONS Together these findings show that MSCs exhibit profound , yet differential , effects on CSC migration , proliferation , and differentiation and suggest a mechanism underlying the improved cardiac regeneration associated with combination therapy using CSCs and MSCs . These findings have important therapeutic implication s for cell-based therapy strategies that use mixtures of CSCs and MSCs BACKGROUND Although human mesenchymal stem cells ( hMSCs ) have been tested in ischemic cardiomyopathy , few studies exist in chronic nonischemic dilated cardiomyopathy ( NIDCM ) . OBJECTIVES The authors conducted a r and omized comparison of safety and efficacy of autologous ( auto ) versus allogeneic ( allo ) bone marrow-derived hMSCs in NIDCM . METHODS Thirty-seven patients were r and omized to either  allo- or auto-hMSCs  in a 1:1 ratio . Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital . Patients received hMSCs ( 100 million ) by transendocardial stem cell injection in 10 left ventricular sites . Treated patients were evaluated at baseline , 30 days , and 3- , 6- , and 12-months for safety ( serious adverse events [ SAE ] ) , and efficacy endpoints : ejection fraction , Minnesota Living with Heart Failure Question naire , 6-min walk test , major adverse cardiac events , and immune biomarkers . RESULTS There were no 30-day treatment-emergent SAEs . Twelve-month SAE incidence was 28.2 % with allo-hMSCs versus 63.5 % with auto-hMSCs ( p = 0.1004 for the comparison ) . One allo-hMSC patient developed an elevated ( > 80 ) donor-specific calculated panel reactive antibody level . The ejection fraction increased in allo-hMSC patients by 8.0 percentage points ( p = 0.004 ) compared with 5.4 with auto-hMSCs ( p = 0.116 ; allo vs. auto p = 0.4887 ) . The 6-min walk test increased with allo-hMSCs by 37.0 m ( p = 0.04 ) , but not auto-hMSCs at 7.3 m ( p = 0.71 ; auto vs. allo p = 0.0168 ) . MLHFQ score decreased in allo-hMSC ( p = 0.0022 ) and auto-hMSC patients ( p = 0.463 ; auto vs. allo p = 0.172 ) . The major adverse cardiac event rate was lower , too , in the allo group ( p = 0.0186 vs. auto ) . Tumor necrosis factor-α decreased ( p = 0.0001 for each ) , to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months ( p = 0.05 ) . CONCLUSIONS These findings demonstrated safety and clinical ly meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients . Pivotal trials of allo-hMSCs are warranted based on these results . ( Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [ PoseidonDCM ] ; NCT01392625 ) Rationale : Potential benefits of mesenchymal stem cell ( MSC ) therapy in heart failure may be related to paracrine properties and systemic effects , including anti-inflammatory activities . If this hypothesis is valid , intravenous administration of MSCs should improve outcomes in heart failure , an entity in which excessive chronic inflammation may play a pivotal role . Objective : To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs ( itMSCs ) in patients with nonischemic cardiomyopathy . Methods and Results : This was a single-blind , placebo-controlled , crossover , r and omized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction ⩽40 % and absent hyperenhancement on cardiac magnetic resonance imaging . Patients were r and omized to intravenously administered itMSCs ( 1.5 × 106 cells/kg ) or placebo ; at 90 days , each group received the alternative treatment . Overall , 22 patients were r and omized  to itMSC  ( n=10 ) and placebo ( n=12 ) at baseline . After crossover , data were available for 22 itMSC patients . No major differences in death , hospitalization , or serious adverse events were noted between the 2 treatments . Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies . Compared with placebo , itMSC therapy increased 6-minute walk distance ( + 36.47 m , 95 % confidence interval 5.98–66.97 ; P=0.02 ) and improved Kansas City Cardiomyopathy clinical summary ( + 5.22 , 95 % confidence interval 0.70–9.74 ; P=0.02 ) and functional status scores ( + 5.65 , 95 % confidence interval −0.11 to 11.41 ; P=0.06 ) . The data demonstrated MSC-induced immunomodulatory effects , the magnitude of which correlated with improvement in left ventricular ejection fraction . Conclusions : In this pilot study of patients with nonischemic cardiomyopathy , itMSC therapy was safe , caused immunomodulatory effects , and was associated with improvements in health status and functional capacity . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT02467387 RATIONALE Allogeneic mesenchymal precursor cells ( MPCs ) have been effective in large animal models of ischemic and nonischemic heart failure ( HF ) . OBJECTIVE To evaluate the feasibility and safety of 3 doses ( 25 , 75 , or 150 million cells ) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial . METHODS AND RESULTS We sequentially allocated 60 patients to a dosing cohort ( 20 per dose group ) and r and omized them to transendocardial MPC injections ( n=15 ) or mock procedures ( n=5 ) . The primary objective was safety , including antibody testing . Secondary efficacy end points included major adverse cardiac events ( MACE ; cardiac death , myocardial infa rct ion , or revascularization ) , left ventricular imaging , and other clinical -event surrogates . Safety and MACE were evaluated for up to 3 years . MPC injections were feasible and safe . Adverse events were similar across groups . No clinical ly symptomatic immune responses were noted . MACE was seen in 15 patients : 10 of 45 ( 22 % ) MPC-treated and 5 of 15 ( 33 % ) control patients . We found no differences between MPC-treated and control patients in survival probability , MACE-free probability , and all-cause mortality . We conducted a post hoc analysis of HF-related MACE ( HF hospitalization , successfully resuscitated cardiac death , or cardiac death ) and events were significantly reduced in the 150 million MPC group ( 0/15 ) versus control ( 5/15 ; 33 % ) , 25 million MPC group ( 3/15 ; 20 % ) , and 75 million MPC group ( 6/15 ; 40 % ) ; the 150 million MPC group differed significantly from all groups according to Kaplan-Meier statistics > 3 years ( P=0.025 for 150 million MPC group versus control ) . CONCLUSIONS Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients . High-dose allogeneic MPCs may provide benefits in this population BACKGROUND The infa rct size determines the long-term prognosis of patients with acute myocardial infa rct ion ( AMI ) . There is a growing interest in repairing scar area by transplanting bone marrow stem cells . However , effectiveness of intracor 
    Output:
    
Conclusions Our results suggested that MSC treatment is an effective therapy for HF by improving the prognosis and exercise capacity .
SCs derived from allosomes have superior therapeutic effects , and intracoronary injection is the optimum MSC delivery approach .
Short-term cryopreservation is feasible in MSCs storage or transport