title: Safety and efficacy of intracoronary hypoxia-preconditioned bone marrow mononuclear cell administration for acute myocardial infarction patients: The CHINA-AMI randomized controlled trial.
abstract: BACKGROUND
  Pre-clinical studies have shown that hypoxia preconditioning can enhance stem cell therapeutic potential for myocardial repair. We sought to investigate the safety and feasibility of intracoronary administration of hypoxia-preconditioned bone marrow mononuclear cells (HP-BMCs) for acute ST segment elevation myocardial infarction (STEMI).
  
  
  METHODS
  We randomized 22 patients with acute STEMI to receive intracoronary administration of normoxia bone marrow mononuclear cells (N-BMCs) (n=11) or HP-BMCs (n=11) following successful reperfusion. Another 14 patients receiving standard therapy were recruited as control (n=14).
  
  
  RESULTS
  There were no differences in the occurrence of major adverse cardiovascular events at 30 days and 1 year among three groups. There were significant improvement in the change of left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in HP-BMC group both at 6 and 12 months compared with N-BMCs or control group (P<0.05). No differences were observed in the change of left ventricular ejection fraction (LVEF), or wall motion score index (WMSI) among three groups. Nevertheless, WMSI was improved in HP-BMCs and N-BMC group (P<0.05, within group), but not in control. The ratio of myocardial perfusion defect determined by SPECT was significantly decreased in HP-BMCs and N-BMC groups at 6months compared with baseline (P<0.05, within group), but no significant differences were observed among three groups.
  
  
  CONCLUSIONS
  Our results provide the first-in-man evidence that intracoronary administration of HP-BMCs following acute MI appears to be safe and feasible. These results provide the basis for future prospective randomized clinical trials in a larger patient cohort.
  
  
  BACKGROUND
  NCT01234181 (http://clinicaltrials.gov/ct2/show/NCT01234181?term=NCT01234181&rank=1).
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China; Department of ultrasonography, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of radiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Nuclear Medicine, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhan
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Jianjing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of ultrasonography, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Pu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Xiang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Yu
authors.affiliation: Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China.
authors.forename: Zexin
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Cardiology Division, Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong, HKSAR, PR China; Shenzhen Institutes of Research and Innovation, the University of Hong Kong, Hong Kong SAR, PR China.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China. Electronic address: jian_an_wang@yahoo.com.
authors.forename: Jian'an
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000098:blood supply*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003331:Coronary Vessels; D004452:Echocardiography / Q000379:methods; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial / Q000379:methods; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery; D013318:Stroke Volume; D016896:Treatment Outcome
keywords: Acute myocardial infarction; Bone marrow mononuclear cells; Hypoxia-preconditioning