Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia

Atsuhiko Kawamoto, Tengis Tkebuchava, Jun Ichi Yamaguchi, Hiromi Nishimura, Young Sup Yoon, Charles Milliken, Shigeki Uchida, Osamu Masuo, Hideki Iwaguro, Hong Ma, Allison Hanley, Marcy Silver, Marianne Kearney, Douglas W. Losordo, Jeffrey M. Isner, Takayuki Asahara

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Abstract

Background - We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia. Methods and 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 107 NA/CD31+ MNCs, 107 NA/CD31- MNCs, or PBS was performed with a NOGA mapping injection catheter to target ischemic myocardium. In a parallel study, 105 human CD34+ MNCs, 105 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.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalCirculation
Volume107
Issue number3
DOIs
Publication statusPublished - 2003 Jan 28

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Kawamoto, A., Tkebuchava, T., Yamaguchi, J. I., Nishimura, H., Yoon, Y. S., Milliken, C., Uchida, S., Masuo, O., Iwaguro, H., Ma, H., Hanley, A., Silver, M., Kearney, M., Losordo, D. W., Isner, J. M., & Asahara, T. (2003). Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation, 107(3), 461-468. https://doi.org/10.1161/01.CIR.0000046450.89986.50