Research Project
2864918
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.
