Genetic and Tissue Engineering for Aneurysms

描述(申请人提供)：这项研究计划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来改善脑(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30,000名患者因破裂而发病率和死亡率受到影响。随着铂金微弹簧圈的发展，治疗此类动脉瘤的高侵入性、开放式脑外科手术的需求已部分减少；这些弹簧圈可以通过小型、灵活的微导管插入脑动脉瘤，从而避免了开放手术。不幸的是，这些微弹簧圈不能在体内诱导细胞增殖和基质沉积，从而导致动脉瘤的永久闭塞。在目前的技术中，微弹簧圈治疗后动脉瘤的再生长仍然很常见。在这项提案中，我们将通过基因和组织工程的方法来解决这一重要的临床问题。我们将通过使用微弹簧圈作为同种异体成纤维细胞移植的载体来增强微弹簧圈在动脉瘤腔内诱导细胞增殖的能力。此外，通过体外基因转移技术，我们将增强植入的同种异体细胞移植合成和分泌胶原的能力，这将有助于加固动脉瘤腔。最后，我们将通过使用新的、炎症最小的“空”腺病毒来改进这种用于动脉瘤治疗的基因和组织工程学方法。我们的研究计划横跨基础科学和技术，代表了一种高度集中的方法，旨在解决持续存在的、明确定义的临床问题。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的患者的护理。

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.