Genetic and Tissue Engineering for Aneurysms

描述（由申请人提供）：本研究项目的长期目标是通过将基因和组织工程与现代医疗设备技术相结合，改善对脑动脉瘤患者的护理。脑动脉瘤是一个重要的临床问题，在美国，每年有3万名患者因破裂而发病和死亡。由于铂微线圈的发展，治疗此类动脉瘤的高侵入性、开放性脑外科手术的需求已经部分减少；这些线圈可以通过小而灵活的微导管置入脑动脉瘤，避免开腹手术。不幸的是，这些微线圈不能诱导体内细胞增殖和基质沉积，从而导致动脉瘤的永久闭塞。在目前的技术下，微线圈治疗后动脉瘤的再生仍然很常见。在这个建议中，我们将通过基因和组织工程的方法来解决这个重要的临床问题。我们将利用微线圈作为成纤维细胞同种异体移植物的载体，增强微线圈诱导动脉瘤腔内细胞增殖的能力。此外，通过体外基因转移技术，我们将增强植入的细胞异体移植物合成和分泌胶原蛋白的能力，这将有助于加强动脉瘤腔。最后，我们将通过使用新的、炎症最小的“空”腺病毒来改进这种基因和组织工程方法来治疗动脉瘤。我们的研究项目交叉了基础科学和技术，代表了一种高度集中的方法，旨在解决一个持久的、明确的临床问题。这项研究计划的成功实施将推动基因和组织工程领域的发展，并将改善对患有危及生命的脑动脉瘤患者的护理。

DESCRIPTION (provided by applicant): The long term goal of this research program is to improve care of patients harboring cerebral (brain) aneurysms by combining genetic and tissue engineering with modern medical device technology. Cerebral aneurysms represent an important clinical problem, with rupture-induced morbidity and mortality affecting 30,000 patients per year in the US. The need for highly invasive, open brain surgery for treatment of such aneurysms has been partially reduced by development of platinum microcoils; these coils can be placed through small, flexible microcatheters into brain aneurysms, avoiding open surgery. Unfortunately, these microcoils fail to induce in vivo cellular proliferation and matrix deposition that would lead to permanent occlusion of aneurysms. Regrowth of aneurysms after microcoil therapy remains common with current technologies. In this proposal we will address this important clinical problem through a genetic and tissue engineering approach. We will enhance the ability of microcoils to induce cellular proliferation within aneurysm cavities by using such coils as carriers of fibroblast allografts. Further, through in vitro gene transfer techniques, we will enhance the ability of implanted cellular allografts to synthesize and secrete collagen, which will serve to reinforce the aneurysm cavity. Last, we will improve this genetic and tissue engineering approach to aneurysm therapy by use of new, minimally inflammatory "empty" adenoviruses. Our research program cross-cuts basic science and technology and represents a highly focused approach aimed at a persistent, well-defined clinical problem. Successful implementation of this research program will advance the field of genetic and tissue engineering and will improve the care of patients harboring life-threatening cerebral aneurysms.