ENDOTHELIAL PROGENITOR CELLS FOR ENGINEERING VESSELS

工程船舶用内皮祖细胞

• 批准号: 7188835
• 负责人: James Koudy Williams
• 金额: $ 16.72万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-05 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7188835
• 关键词: Address; Age; Arteries; Autologous; Award; Berry; Biology; Biomechanics; Biomedical Engineering; Bioreactors; Blood Vessels; Bone Marrow; Bypass; Calculi; Cardiovascular Diseases; Carotid Arteries; Cells; Collaborations; Collagen; Condition; Coronary Artery Bypass; Development; Development Plans; Disease; Disease susceptibility; Endothelium; Evaluation; Facility Construction Funding Category; Failure; Future; Human; Individual; Institutes; Medical; Medical Research; Methodology; Monkeys; Operative Surgical Procedures; Patients; Peripheral; Phylogenetic Analysis; Physiological; Population; Prevention approach; Primates; Procedures; Property; Regenerative Medicine; Research; Research Personnel; Scientist; Sheep; Source; Stem Cell Research; Stem cells; Testing; Time; Today; Transplanted tissue; United States; Universities; Vascular Diseases; Vascular Graft; Work; base; career; cellular engineering; clinical application; cost; desire; disability; forest; hemodynamics; in vivo; new technology; nonhuman primate; preconditioning; scaffold; stem

DESCRIPTION (provided by applicant): This Career Enhancement Award in Stem Cell Research will enable Dr. J. Koudy Williams to re-direct his research to stem cell approaches for the prevention and treatment of vascular disease. The proposed research plan combines the stem cell/regenerative medicine expertise of the Wake Forest University Institute of Regenerative Medicine (WFIRM) with the vascular biology/surgical expertise of Dr. Williams. Dr. Williams has institutional support for this award and has selected Dr. Shay Soker - a WFIRM core scientist whose expertise is the use of stem/progenitor cells in vascular research - as his sponsor. Dr. Williams has chosen co-investigators with expertise in vascular surgery (Dr. Geary), and biomechanics (Dr. Berry) who, with Dr. Soker, have devised a career development plan facilitating his current and future work in stem cell research. Over 500,000 coronary artery bypass grafts and 50,000 peripheral bypass grafts are performed annually in the United States due, in part, to complications of atherosclerotic disease. However, up to 30% of patients requiring arterial bypass surgery and other vascular procedures lack suitable or sufficient amounts of autologous graft material. We have shown that endothelial progenitor cells (EPCs) provide an endothelium and promote patency of bioengineered arteries for more than 4 months when used as carotid artery interposition grafts in sheep. However, the construction conditions of EPC-seeded bioengineered blood vessels in primates are currently unknown. The utility of primates in this research is critical because of their close phylogenetic, vascular disease susceptibility, and physiologic similarities to those of human beings. Our working hypothesis is that bioengineered blood vessels made from collagen scaffolds seeded with monkey EPCs and then used autologously to create an interpositional arterial graft will adapt to physiological flow conditions and mature in vivo to assume normal properties of native arteries. To address these questions, and test this hypothesis, we propose the following specific aims: 1) To construct blood vessels from collagen scaffolds seeded with EPCs from the bone marrow of monkey; and then 2) To examine the structural and functional properties of bioengineered vascular grafts when placed in nonhuman primates. Future directions of this research will be to extend this methodology to atherosclerotic nonhuman primates and examine the mechanisms regulating remodeling of the maturing bioengineered grafts. The proposed studies represent a stepping stone to the development of blood vessels to be used by individuals needing coronary artery bypass surgery, peripheral vascular surgery, and other vascular disorders. As such, these studies are an exciting and unique direction of research for Dr. Williams in collaboration with his colleagues at WFIRM.

描述（由申请人提供）：这项干细胞研究职业提升奖将使J. Koudy威廉姆斯博士能够重新指导他的研究，以干细胞方法预防和治疗血管疾病。拟议的研究计划将维克森林大学再生医学研究所（WFIRM）的干细胞/再生医学专业知识与威廉姆斯博士的血管生物学/外科专业知识相结合。威廉姆斯博士获得了该奖项的机构支持，并选择了Shay Soker博士作为他的赞助人。Shay Soker博士是WFIRM的核心科学家，其专长是在血管研究中使用干细胞/祖细胞。威廉姆斯博士选择了在血管外科（Geary博士）和生物力学（Berry博士）方面具有专业知识的合作研究者，他们与Soker博士一起设计了一个职业发展计划，以促进他目前和未来在干细胞研究方面的工作。在美国每年进行超过500，000例冠状动脉旁路移植术和50，000例外周旁路移植术，部分原因是动脉粥样硬化疾病的并发症。然而，高达30%的需要动脉旁路手术和其他血管手术的患者缺乏合适或足够量的自体移植材料。我们已经证明，内皮祖细胞（EPCs）提供了一个内皮和促进通畅的生物工程动脉超过4个月时，用作颈动脉间置移植物在绵羊。然而，EPC种子生物工程血管在灵长类动物中的构建条件目前尚不清楚。灵长类动物在这项研究中的效用是至关重要的，因为它们与人类有着密切的系统发育、血管疾病易感性和生理相似性。我们的工作假设是，由接种有猴EPCs的胶原支架制成的生物工程血管，然后自体用于创建插入动脉移植物，将适应生理流动条件并在体内成熟以呈现天然动脉的正常特性。为了解决这些问题，并验证这一假设，我们提出了以下具体目标：1）从接种有来自猴骨髓的EPCs的胶原支架构建血管;然后2）当放置在非人灵长类动物中时，检查生物工程血管移植物的结构和功能特性。这项研究的未来方向将是将这种方法扩展到动脉粥样硬化的非人灵长类动物，并检查成熟的生物工程移植物的重塑调节机制。拟议的研究代表了需要冠状动脉搭桥手术、外周血管手术和其他血管疾病的个体所使用的血管的开发的垫脚石。因此，这些研究是威廉姆斯博士与WFIRM同事合作的一个令人兴奋和独特的研究方向。