title: Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: phase I clinical study.
abstract: BACKGROUND
  MultiStem is an allogeneic bone marrow-derived adherent adult stem cell product that has shown efficacy in preclinical models of acute myocardial infarction (AMI). In this phase I clinical trial in patients with first ST-elevation-myocardial infarction (STEMI), we combine first-in-man delivery of MultiStem with a first-in-coronary adventitial delivery system to determine the effects of this system on left ventricular function at 4 months after AMI.
  
  
  OBJECTIVE
  Test the effects of adventitial delivery of Multistem in the peri-infarct period in patients with first STEMI.
  
  
  RESULTS
  This study was a phase I, open-label, dose-escalating registry control group study. Nineteen patients received MultiStem (20 million, n=6; 50 million, n=7; or 100 million, n=6) and 6 subjects were assigned to the registry control group. Two to 5 days after AMI, we delivered MultiStem to the adventitia of the infarct-related vessel in patients with first-time STEMI. All patients underwent primary percutaneous coronary intervention with resulting Thrombolysis In Myocardial Infarction grade 3 flow and with ejection fraction (EF) ≤45% as determined by echocardiogram or left ventriculogram within 12 hours of primary percutaneous coronary intervention. The cell product (20 million, 50 million, or 100 million) was well tolerated, and no serious adverse events were deemed related to MultiStem. There was no increase in creatine kinase-MB or troponin associated with the adventitial delivery of MultiStem. In patients with EF determined to be ≤45% by a core laboratory within 24 hours before the MultiStem injection, we observed a 0.9 (n=4), 3.9 (n=4), 13.5 (n=5), and 10.9 (n=2) percent absolute increases in EF in the registry, 20 million, 50 million, and 100 million dose groups, respectively. The increases in EF in the 50 million and 100 million groups were accompanied by 25.4 and 8.4 mL increases in left ventricular stroke volume.
  
  
  CONCLUSIONS
  In this study, the delivery of MultiStem to the myocardium in patients with recent STEMI was well tolerated and safe. In patients who exhibited significant myocardial damage, the delivery of ≥50 million MultiStem resulted in improved EF and stroke volume 4 months later. These findings support further development of MultiStem in patients with AMI and they validate the potential of a system for delivery of adult stem cells at any time after primary percutaneous coronary intervention.
authors: Summa Cardiovascular Institute, 525 E. Market St., Akron, OH 44309, USA. pennms@summahealth.org
authors: Marc S
authors: MS
authors: Penn
authors: Stephen
authors: S
authors: Ellis
authors: Sanjay
authors: S
authors: Gandhi
authors: Adam
authors: A
authors: Greenbaum
authors: Zachary
authors: Z
authors: Hodes
authors: Farrell O
authors: FO
authors: Mendelsohn
authors: David
authors: D
authors: Strasser
authors: Anthony E
authors: AE
authors: Ting
authors: Warren
authors: W
authors: Sherman
mesh_terms: D053687:Adult Stem Cells / Q000276:immunology / Q000637:transplantation*; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D003131:Combined Modality Therapy; D003238:Connective Tissue; D005260:Female; D006801:Humans; D008297:Male; D008845:Microinjections; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D020127:Recovery of Function; D012042:Registries; D013318:Stroke Volume; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014481:United States; D016277:Ventricular Function, Left