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

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Autologous Transplantation
Myocardial Ischemia
Therapeutics
Myocardium
Catheters
Endothelial Progenitor Cells
Swine
Transplantation
Nude Rats
Control Groups
Injections
Left Ventricular Function
Stroke Volume
Ligation

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Kawamoto, Atsuhiko ; Tkebuchava, Tengis ; Yamaguchi, Jun Ichi ; Nishimura, Hiromi ; Yoon, Young Sup ; Milliken, Charles ; Uchida, Shigeki ; Masuo, Osamu ; Iwaguro, Hideki ; Ma, Hong ; Hanley, Allison ; Silver, Marcy ; Kearney, Marianne ; Losordo, Douglas W. ; Isner, Jeffrey M. ; Asahara, Takayuki. / Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. In: Circulation. 2003 ; Vol. 107, No. 3. pp. 461-468.
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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.",
author = "Atsuhiko Kawamoto and Tengis Tkebuchava and Yamaguchi, {Jun Ichi} and Hiromi Nishimura and Yoon, {Young Sup} and Charles Milliken and Shigeki Uchida and Osamu Masuo and Hideki Iwaguro and Hong Ma and Allison Hanley and Marcy Silver and Marianne Kearney and Losordo, {Douglas W.} and Isner, {Jeffrey M.} and Takayuki Asahara",
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Kawamoto, A, Tkebuchava, T, Yamaguchi, JI, Nishimura, H, Yoon, YS, Milliken, C, Uchida, S, Masuo, O, Iwaguro, H, Ma, H, Hanley, A, Silver, M, Kearney, M, Losordo, DW, Isner, JM & Asahara, T 2003, 'Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia', Circulation, vol. 107, no. 3, pp. 461-468. https://doi.org/10.1161/01.CIR.0000046450.89986.50

Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. / Kawamoto, Atsuhiko; Tkebuchava, Tengis; Yamaguchi, Jun Ichi; Nishimura, Hiromi; Yoon, Young Sup; Milliken, Charles; Uchida, Shigeki; Masuo, Osamu; Iwaguro, Hideki; Ma, Hong; Hanley, Allison; Silver, Marcy; Kearney, Marianne; Losordo, Douglas W.; Isner, Jeffrey M.; Asahara, Takayuki.

In: Circulation, Vol. 107, No. 3, 28.01.2003, p. 461-468.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia

AU - Kawamoto, Atsuhiko

AU - Tkebuchava, Tengis

AU - Yamaguchi, Jun Ichi

AU - Nishimura, Hiromi

AU - Yoon, Young Sup

AU - Milliken, Charles

AU - Uchida, Shigeki

AU - Masuo, Osamu

AU - Iwaguro, Hideki

AU - Ma, Hong

AU - Hanley, Allison

AU - Silver, Marcy

AU - Kearney, Marianne

AU - Losordo, Douglas W.

AU - Isner, Jeffrey M.

AU - Asahara, Takayuki

PY - 2003/1/28

Y1 - 2003/1/28

N2 - 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.

AB - 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.

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U2 - 10.1161/01.CIR.0000046450.89986.50

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JF - Circulation

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