ENDOTHELIAL PROGENITOR CELLS FOR ENGINEERING VESSELS

工程船舶用内皮祖细胞

• 批准号: 7350152
• 负责人: James Koudy Williams
• 金额: $ 17.06万
• 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/7350152
• 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; 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）：干细胞研究中的这一职业增强奖将使J. Koudy Williams博士能够将他的研究重新指导为预防和治疗血管疾病的干细胞方法。拟议的研究计划将Wake Forest大学再生医学研究所（WFIRM）的干细胞/再生医学专业知识与Williams博士的血管生物学/外科专业知识相结合。威廉姆斯博士对该奖项拥有机构支持，并选择了Shay Soker博士（WFIRM核心科学家，其专业知识是使用STEM/祖细胞在血管研究中的使用 - 作为他的赞助商。威廉姆斯博士选择了具有血管外科专业知识（Geary博士）和生物力学（Berry博士）的共同研究人员，他们与Soker博士一起制定了一项职业发展计划，以促进他目前和未来的干细胞研究工作。每年在美国每年进行500,000多个冠状动脉旁路移植物和50,000个外围旁路移植物，部分原因是动脉粥样硬化疾病的并发症。但是，需要动脉搭桥手术和其他血管手术的患者中，多达30％的患者缺乏适当或足够数量的自体移植物材料。我们已经表明，当用作绵羊中的颈动脉介入移植物时，内皮祖细胞（EPC）提供了内皮并促进生物工程动脉的通畅4个月以上。但是，目前尚不清楚通过灵长类动物中EPC种子生物工程血管的结构条件。灵长类动物在这项研究中的效用至关重要，因为它们的系统发育，血管疾病的敏感性紧密，并且与人类的生理相似性。我们的工作假设是，用猴子EPC播种的胶原蛋白支架制成的生物工程血管，然后自体用来创建螺旋性动脉移植物，将适应生理流动条件和体内成熟的体内，以假设天然动脉的正常特性。为了解决这些问题，并检验了这一假设，我们提出了以下具体目的：1）从猴子骨髓中用EPC播种的胶原蛋白支架的血管构建血管；然后2）将生物工程性血管移植物的结构和功能特性检查放置在非人类灵长类动物中时。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类灵长类动物，并检查调节成熟生物工程移植物重塑的机制。拟议的研究代表了需要冠状动脉搭桥手术，周围血管外科手术和其他血管疾病的个体使用的血管发展的垫脚石。因此，这些研究是威廉姆斯博士与WFIRM的同事合作的一个令人兴奋而独特的研究方向。