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对于多种生理和病理过程必不可少，主要使用动物模型或动物衍生的杀伤力系统研究。不幸的是，这些模型表现出组成复杂性和生物学局限性。此外，没有其他明确定义的实验模型可用于研究人类中离散的血管细胞 - 髓相互作用。因此，我们创建了一种新型的人类细胞外矩阵（ECM），AMGEL，该基质源自探索各种人类细胞的调节和功能行为的细胞羊膜。 Amgel Biomatrix的标志包括其无生长因子和无蛋白酶状态以及存在生物活性的主要人类基质成分。我们建议开发定义或控制的Amgel Biomatrix系统，以检查人类新血管化过程的早期至晚期，即内皮细胞增殖，运动性和分化。这项工作将有两个具体的目标：l。通过富集特定生长因子，纯化的ECM蛋白和合成肽来开发和优化定义的人类Biomatrix系统。 2。证明AMGEL矩阵在人血管细胞增殖，迁移和分化生物测定中的实际应用。总体目标是使用定义的AMGEL矩阵开发和商业化新的人类生物测定系统。这种人类血管模型（人造血管系统）将有助于：l）评估人类细胞/组织衍生因子的有丝分裂，动作和分化反应； 2）筛选促和抗血管生成剂的潜力； 3）为动物研究提供了一种新的替代方法，并直接洞悉了Neovessel形成过程的控制点。 Amgel的独特环境使人们可以在生理和病理状况下检查人类细胞和细胞 - 玛尔底相互作用及其调节。因此，这种新的人类Biomatrix模型系统的商业化具有巨大的潜力，该模型来自正常组织用于生物医学研究。拟议的商业应用：目前不存在使用定义的人类生物机系统的可接受的体外生物测定法。我们将开发，优化和评估可重复使用和一次性Amgel Biomatrix系统。每年数十万美元，销售AMGEL和预包装的测定系统可能会在全球范围内作为研究和诊断工具。这将影响组织工程和血管疾病的领域。