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

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）：干细胞研究领域的职业发展奖将使 J. Koudy Williams 博士能够将他的研究重新转向干细胞方法，以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 Williams 博士的血管生物学/外科专业知识相结合。 Williams 博士获得了该奖项的机构支持，并选择 Shay Soker 博士（WFIRM 核心科学家，其专业知识是在血管研究中使用干/祖细胞）作为赞助商。 Williams 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联合研究人员，他们与 Soker 博士一起制定了职业发展计划，以促进他当前和未来在干细胞研究方面的工作。美国每年进行超过 500,000 例冠状动脉搭桥术和 50,000 例外周搭桥术，部分原因是动脉粥样硬化性疾病的并发症。然而，高达 30% 需要动脉搭桥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 (EPC) 用作绵羊颈动脉介入移植物时，可提供内皮并促进生物工程动脉的通畅超过 4 个月。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应用至关重要，因为它们与人类有密切的系统发育、血管疾病易感性以及生理相似性。我们的工作假设是，由接种猴 EPC 的胶原蛋白支架制成的生物工程血管，然后自体用于创建插入式动脉移植物，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检验这一假设，我们提出以下具体目标：1）用接种了猴骨髓 EPC 的胶原蛋白支架构建血管；然后 2) 检查生物工程血管移植物置于非人类灵长类动物体内时的结构和功能特性。这项研究的未来方向是将这种方法扩展到动脉粥样硬化的非人灵长类动物，并研究调节成熟生物工程移植物重塑的机制。拟议的研究为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开发血管奠定了基础。因此，这些研究是 Williams 博士与 WFIRM 同事合作的一个令人兴奋且独特的研究方向。

项目成果

The effects of ethanol consumption on vasculogenesis potential in nonhuman primates.

乙醇消耗对非人灵长类动物血管生成潜力的影响。

• DOI: 10.1111/j.1530-0277.2007.00558.x
• 发表时间: 2008
• 期刊: Alcoholism, clinical and experimental research
• 作者: Williams,JKoudy;Baptista,PedroM;Daunais,JamesB;Szeliga,KendallT;Friedman,DavidP;Soker,Shay
• 通讯作者: Soker,Shay