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DEFINED BIOMATRIX MODEL FOR HUMAN VASCULAR STUDIES

用于人类血管研究的定义生物基质模型

基本信息

批准号：
2864918
负责人：
GAYLE K CHRISTOPHER
金额：
$ 10万
依托单位：
DIVERSIFIED SCIENTIFIC, INC.
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-05-01 至 2000-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2864918
关键词：
amnion artificial membranes bioassay biological models cell cell interaction cell differentiation cell migration cell proliferation extracellular matrix extracellular matrix proteins growth factor human tissue model design /development synthetic peptide technology /technique development tissue /cell culture vascular endothelium

项目摘要

Vascular cell proliferation and differentiation, essential for multiple physiological and pathological processes, are mostly studied using animal models or animal-derived biomatrix systems. Unfortunately, these models exhibit compositional complexity and biological limitations. Moreover, no other well defined experimental model is available for studying the discrete vascular cell-matrix interactions in humans. We have, therefore, created a novel human extracellular' matrix (ECM), Amgel, derived from acellular amnions for exploring the regulatory and functional behavior of a variety of human cells. The hallmarks of Amgel biomatrix include its growth factor-free and protease-free status and the presence of major human matrix components of biological activity. We propose to develop defined or controlled Amgel biomatrix systems for examining the early to late stages of the human neovascularization process i.e. endothelial cell proliferation, motility and differentiation. This effort will have two specific objectives: l. To develop and optimize defined human biomatrix systems by enrichment of Amgel with specific growth factors, purified ECM proteins and synthetic peptides. 2. To demonstrate the practical applications of Amgel matrices in human vascular cell proliferation, migration and differentiation bioassays. The overall goal is to develop and commercialize new human bioassay systems employing defined Amgel matrices. This human vascular model (artificial vessel system) will be useful for: l) evaluating the mitogenic, motogenic and differentiation responses of human cell/tissue-derived factors; 2) screening the potential of pro- and anti-angiogenic agents; and 3) providing a new alternative to animal studies with a direct insight into the control-points of neovessel formation process. Amgel's unique environment allows one to examine human cell-cell and cell-matrix interactions and their modulation under both physiologic and pathologic conditions. Thus, there is significant potential for the commercialization of this new human biomatrix model system derived from normal tissues for use in biomedical research. PROPOSED COMMERCIAL APPLICATIONS: No acceptable commercial in vitro bioassay currently exists which utilizes a defined human biomatrix system. We will develop, optimize and evaluate reusable and disposable Amgel biomatrix systems. Sale of Amgel and pre-packed assay systems could have a potential world-wide market, both as a research and diagnostic tool, in the hundreds of thousands of dollars/year. This will impact the fields of tissue engineering and vascular diseases.

血管细胞的增殖和分化是多种生理和病理过程所必需的，目前主要是通过动物模型或动物源性生物基质系统进行研究。不幸的是，这些模型表现出成分的复杂性和生物学的局限性。此外，没有其他明确的实验模型可用于研究人类血管细胞-基质的离散相互作用。因此，我们创造了一种新的人类细胞外基质（ECM）， Amgel，来源于脱细胞羊膜，用于探索各种人类细胞的调节和功能行为。Amgel生物基质的特点包括其无生长因子和无蛋白酶状态，以及主要人类基质生物活性成分的存在。我们建议开发定义或控制的Amgel生物基质系统，用于检查人类新生血管过程的早期到晚期阶段，即内皮细胞增殖，运动和分化。这项工作将有两个具体目标：1 .通过用特定生长因子、纯化的ECM蛋白和合成肽富集Amgel来开发和优化定义的人类生物基质系统。2. 演示安格尔基质在人血管细胞增殖、迁移和分化生物测定中的实际应用。总体目标是开发和商业化新的人类生物测定系统，使用定义的Amgel矩阵。这种人体血管模型（人造血管系统）将有助于：1)评估人类细胞/组织源性因子的有丝分裂、运动和分化反应；2)筛选促血管生成和抗血管生成药物的潜力；3)提供了一种新的替代动物研究，直接洞察新血管形成过程的控制点。安格尔独特的环境允许人们检查人类细胞-细胞和细胞-基质相互作用及其在生理和病理条件下的调节。因此，这种从正常组织中提取的新型人体生物基质模型系统在生物医学研究中具有巨大的商业化潜力。拟议的商业应用：目前没有可接受的商业体外生物测定法，它利用了定义的人类生物基质系统。我们将开发、优化和评估可重复使用和一次性安吉尔生物基质系统。作为研究和诊断工具，Amgel和预包装检测系统的销售可能具有潜在的全球市场，年销售额可达数十万美元。这将影响组织工程和血管疾病领域。