title: Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia.
abstract: BACKGROUND
  We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia.
  
  
  RESULTS
  Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31+ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31+ MNCs in noncoated plates, nonadhesive cells (NA/CD31+ MNCs) were harvested as the endothelial progenitor cell-enriched fraction. Nonadhesive CD31- cells (NA/CD31- MNCs) were also prepared. Autologous transplantation of 10(7) NA/CD31+ MNCs, 10(7) NA/CD31- MNCs, or PBS was performed with a NOGA mapping injection catheter to target ischemic myocardium. In a parallel study, 10(5) human CD34+ MNCs, 10(5) human CD34- MNCs, or PBS was transplanted into ischemic myocardium of nude rats 10 minutes after ligation of the left anterior descending coronary artery. In the swine study, ischemic area by NOGA mapping, Rentrop grade angiographic collateral development, and echocardiographic left ventricular ejection fraction improved significantly 4 weeks after transplantation of NA/CD31+ MNCs but not after injection of NA/CD31- MNCs or PBS. Capillary density in ischemic myocardium 4 weeks after transplantation was significantly greater in the NA/CD31+ MNC group than the control groups. In the rat study, echocardiographic left ventricular systolic function and capillary density were significantly better preserved in the CD34+ MNC group than in the control groups 4 weeks after myocardial ischemia.
  
  
  CONCLUSIONS
  These favorable outcomes encourage future clinical trials of catheter-based, intramyocardial transplantation of autologous CD34+ MNCs in the setting of chronic myocardial ischemia.
authors.affiliation: Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.forename: Tengis
authors.initials: T
authors.lastname: Tkebuchava
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nishimura
authors.forename: Young-Sup
authors.initials: YS
authors.lastname: Yoon
authors.forename: Charles
authors.initials: C
authors.lastname: Milliken
authors.forename: Shigeki
authors.initials: S
authors.lastname: Uchida
authors.forename: Osamu
authors.initials: O
authors.lastname: Masuo
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwaguro
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Allison
authors.initials: A
authors.lastname: Hanley
authors.forename: Marcy
authors.initials: M
authors.lastname: Silver
authors.forename: Marianne
authors.initials: M
authors.lastname: Kearney
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Losordo
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Isner
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D006328:Cardiac Catheterization; D002454:Cell Differentiation; D019070:Cell Lineage; D002908:Chronic Disease; D017023:Coronary Angiography; D004730:Endothelium, Vascular / Q000166:cytology*; D005355:Fibrosis; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000628:therapy*; D009206:Myocardium / Q000166:cytology*; D018919:Neovascularization, Physiologic; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D013552:Swine; D014463:Ultrasonography; D016277:Ventricular Function, Left
chemical_list: D018952:Antigens, CD34