title: A systematic review of randomised controlled trials examining the therapeutic effects of adult bone marrow-derived stem cells for non-ischaemic dilated cardiomyopathy.
abstract: Certain early-phase clinical trials have suggested that bone marrow-derived stem cell transplantation might improve left ventricular function in patients with non-ischaemic dilated cardiomyopathy (NIDCM), whereas others trials have revealed no benefit from this approach. We sought to evaluate the therapeutic effects of bone marrow-derived stem cell therapy on NIDCM.
  
  
  
  We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (through February 2016) for randomised controlled clinical trials that reported on bone marrow-derived stem cell transplantation for patients with NIDCM with a follow-up period ≥12 months. The co-primary endpoints were changes in mortality rate and left ventricular ejection fraction (LVEF); the secondary endpoints were changes in the 6-minute-walk test (6MWT) and left ventricular chamber size. Seven trials involving bone marrow-derived stem cell therapy that included 482 patients satisfied the inclusion and exclusion criteria.
  
  
  
  Subjects who received bone marrow-derived stem cell therapy exhibited a significant reduction in mortality rate (19.7% in the cell group vs. 27.1% in the control group; 95% confidence interval (CI) -0.16 to -0.00, I2= 52%, p = 0.04). Bone marrow-derived stem cell therapy tended to produce LVEF improvement within 6 months (1.83% increase; 95% CI -0.27 to 3.94, I2= 74%, p = 0.09) and significantly improved LVEF after mid-term (6-12 months) follow-up (3.53% increase; 95% CI 0.76 to 6.29, I2= 88%, p = 0.01). However, this therapy produced no significant benefit in the 6MWT (p = 0.18). Finally, the transplantation of increased numbers of stem cells resulted in no observable additional benefit with respect to LVEF.
  
  
  
  Bone marrow-derived stem cell therapy might have improved prognoses and appeared to provide moderate benefits in cardiac systolic function at mid-term follow-up. However, this therapy produced no observed improvement in exercise tolerance.
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Menglu
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Jiale
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China. jiangmeng0919@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai, 200127, China. heben@medmail.com.cn.
authors.forename: Ben
authors.initials: B
authors.lastname: He
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D001853:Bone Marrow / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods; D002311:Cardiomyopathy, Dilated / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation / Q000379:methods; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
keywords: Bone marrow-derived stem cell therapy; Cardiac systolic function; Follow-up; Mortality rate; Non-ischaemic dilated cardiomyopathy