ORIGIN OF CELLS THAT REPOPULATE RESORBABLE ECM SCAFFOLDS

重新填充可吸收 ECM 支架的细胞的起源

• 批准号: 6387084
• 负责人: Stephen F. Badylak
• 金额: $ 42.53万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6387084
• 关键词: angiogenesis; biodegradable product; biomaterial compatibility; bone marrow transplantation; cell population study; cell type; collagen; extracellular matrix; genetically modified animals; laboratory mouse; tissue engineering; tissue support frame; vascular endothelium

This application is in response to Program Announcement 99-024: Research on Tissue Engineering. The overall goal of our tissue engineering efforts is to develop safe and effective scaffolds that support the restoration of injured or damaged tissues. Specifically, the proposed research will investigate the interaction between acellular, resorbable scaffold/matrices and the cells which repopulate such scaffolds following implantation in mammalian hosts. The central hypothesis of this application is that scaffolds developed from naturally-occurring extracellular matrix (ECM) can recruit circulating progenitor cells which inhabit the scaffold, proliferate, and differentiate into site-specific functional tissues. Two controlled animal studies are proposed; each of which uses two separate mouse models that allow for selective identification of cells which originate in the bone marrow. These studies are designed to successfully accomplish three specific aims: (1) to determine the contribution of circulating progenitor cells to remodeled tissue when naturally-occurring ECMs are used as resorbable scaffolds for tissue repair; (2) to determine the source of endothelial cells which participate in neovascularization of ECM scaffolds; and (3) to determine the effect of adding ECM materials to porous synthetic polymer scaffolds upon neovascularization and the source of endothelial cells which contribute to remodeling. The origin (source) of cells which participate in ECM scaffold remodeling will be compared against the origin of cells which contribute to the remodeling of other acellular resorbable scaffolds; specifically Type I collagen, Alloderm , and poly(L- glycolic acid) (PLGA). Completion of these 3 specific aims will provide important and necessary information for the future intelligent design of scaffolds in a variety of tissue engineering applications; especially those applications where neovascularization is a critical determinant for success. The rationale for the proposed research is based upon extensive preliminary studies, recent findings in progenitor cell biology, an innovative animal model developed by one of the co- investigators, and will be conducted by an experienced interdisciplinary research team in a timely fashion.

本申请是为了响应计划公告 99-024：组织工程研究。 我们组织工程工作的总体目标是开发安全有效的支架来支持受伤或受损组织的修复。具体来说，拟议的研究将调查非细胞、可吸收支架/基质与植入哺乳动物宿主后重新填充此类支架的细胞之间的相互作用。 该应用的中心假设是，由天然存在的细胞外基质（ECM）开发的支架可以招募居住在支架上的循环祖细胞，增殖并分化为特定位点的功能组织。 提出了两项​​对照动物研究；每个模型都使用两个独立的小鼠模型，可以选择性地识别源自骨髓的细胞。 这些研究旨在成功实现三个具体目标：（1）确定当天然存在的 ECM 用作组织修复的可吸收支架时，循环祖细胞对重塑组织的贡献； (2)确定参与ECM支架新生血管形成的内皮细胞来源； (3)确定在多孔合成聚合物支架中添加ECM材料对新生血管形成的影响以及有助于重塑的内皮细胞的来源。 参与 ECM 支架重塑的细胞起源（来源）将与有助于其他非细胞可吸收支架重塑的细胞起源进行比较；特别是 I 型胶原蛋白、Alloderm 和聚（L-乙醇酸）（PLGA）。 这3个具体目标的完成将为未来各种组织工程应用中支架的智能设计提供重要且必要的信息；尤其是那些新血管形成是成功的关键决定因素的应用。 拟议研究的基本原理基于广泛的初步研究、祖细胞生物学的最新发现、由一位共同研究人员开发的创新动物模型，并将由经验丰富的跨学科研究团队及时进行。