Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia

作者：Atsuhiko Kawamoto, Heon-Cheol Gwon, Hideki Iwaguro, Jun‐ichi Yamaguchi, Shigeki Uchida, Haruchika Masuda, Marcy Silver, Hong Ma, Marianne Kearney, Jeffrey M. Isner, Takayuki Asahara · 发表于：Circulation · 年份：2001 · DOI：10.1161/01.cir.103.5.634 · 被引用次数：1225 · 研究领域：Angiogenesis and VEGF in Cancer、Congenital heart defects research、Mesenchymal stem cell research

BACKGROUND: We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. METHODS AND RESULTS: Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 10(6) EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significa...