Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia.
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.
Kawamoto
Atsuhiko
A
Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
Tkebuchava
Tengis
T
Yamaguchi
Jun-Ichi
J
Nishimura
Hiromi
H
Yoon
Young-Sup
YS
Milliken
Charles
C
Uchida
Shigeki
S
Masuo
Osamu
O
Iwaguro
Hideki
H
Ma
Hong
H
Hanley
Allison
A
Silver
Marcy
M
Kearney
Marianne
M
Losordo
Douglas W
DW
Isner
Jeffrey M
JM
Asahara
Takayuki
T
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
D018952:Antigens, CD34