Therapeutic Myocardial Angiogenesis by Catheter-Based Transfer of Vascular Growth Factor Gene and Bone Marrow Stem Cells

對於無法接受繞道手術或經皮冠狀血 管擴張術的冠心症患者其治療目前仍有瓶 頸。將載錄血管生成素的基因轉植入組 織，以刺激血管新生（angiogenesis ）的方 法，已在許多動物心肌缺氧病變模型及人 體實驗上有了令人振奮的結果。在植入基 因的包裝方法包括質體（plasmid ）或病毒 載體（viral vectors ）。在輸送途徑，則有 經冠狀動脈灌流、心包膜內注射及直接注 入心肌等途徑。而血管內皮前驅細胞 （endothelial progenitor cells ）在血管新生 的重要性也漸為所知。如何產生具功能且 持久的血管，無論是在血管生成素的種 類、基因載入方法及運送途徑的選擇上， 仍屬未定之論。我們假設，將載有VEGF165 cDNA 的腺病毒及自體骨髓幹細胞經心導 管術直接注入缺氧心肌，可強化側枝循環 血管生成，改善局部灌流及心肌功能。更 進一步對治療動脈硬化疾病的新要開發有所助益。Therapeutic angiogenesis, in the form of growth factor protein administration or gene therapy, has emerged as a new horizon of the treatment of patients with severe, inoperable coronary artery disease. Improved myocardial perfusion and function after the administration of angiogenic growth factors or gene transfer, such fibroblastic growth factors (FGFs), vascular endothelial growth factors (VEGFs), has been demonstrated in animal models of chronic myocardial ischemia models. Angiogenesis by gene transfer is currently under investigation using a variety of growth factors, the way of gene transfer and a wide array of potential delivery system. These include application of gene as naked DNA, or by viral vector. The deliver systems include intracoronary, intrapericardial, direct intramyocardial techniques. The significance of endothelial progenitor cells in the enhancement of neovascularization is also promising. However, the optimal way to achieve the "functional and sustainable" angiogenesis is still unclear. We propose that administration of replication-deficient adenovirus vector expressing VEGF165 cDNA in combination with vascular endothelial progenitor cells directly into ischemic myocardium which is defined by catheter-based electromechanical mapping would enhance collateral vessel formation, regional myocardial perfusion, and cardiac function