NEW IN VITRO 3D FUNCTIONAL MODEL OF TUMORIGENESIS

描述(由申请人提供)： 需要开发一种模拟肿瘤体内生物学的体外肿瘤发生模型。目前，肿瘤研究主要采用单层细胞培养和动物源性生物基质系统。常用的Matrigel和胶原蛋白模型显示出主要的成分和生物学限制。此外，没有明确定义的功能模型可用于研究人类肿瘤发展的重要阶段。DSI最近创建了一种新的人类生物基质系统HuBiogel，用于探索细胞与基质的相互作用。与现有的模型不同，它的生理基质环境积极支持上皮细胞和内皮细胞的增殖、组织和分化。利用这种通用的BioMatrix技术，DSI建议开发新的与生理相关的(3D)人类肿瘤侵袭和血管生成模型。这些肿瘤-宿主生物检测系统将允许在体外分析肿瘤生长和进展的离散细胞和分子事件。第一阶段的具体目标是：1.使用定义的BioMatrix配方和3D细胞培养配置开发和优化HuBiogel分析系统；2.展示使用多细胞肿瘤球体与成纤维细胞或内皮细胞共培养监测关键肿瘤发生事件的实际应用。在这个研发项目的第二阶段，将扩大新生物检测的功能研究，以便与其他人类肿瘤模型进行验证。这一临床相关模型的及时发展将对癌症生物学、药物发现和治疗领域产生积极影响。商业重要性和意义：目前还没有可接受的使用定义的人类生物矩阵系统的商业肿瘤模型。DSI将开发可重复使用和一次性的3D肿瘤侵袭和血管生成生物检测方法。HuBiogel和预包装化验系统的销售将在全球范围内拥有巨大的市场，无论是作为研究还是诊断工具。

DESCRIPTION (provided by applicant): There is a need for developing an in vitro tumorigenesis model which mimics the in vivo biology of tumors. At present, tumor studies mostly utilize monolayer cell cultures and animal-derived biomatrix systems. The commonly used Matrigel and collagen models exhibit major compositional and biological limitations. Moreover, no well defined functional model is available for examining the important stages of tumor development in humans. DSI recently created a novel human biomatrix system, HuBiogel, for exploring cell-matrix interactions. Its physiologic matrix milieu, unlike existing models, actively supports proliferation, organization and differentiation of epithelial and endothelial cells. Employing this versatile biomatrix technology, DSI proposes to develop new physiologically-relevant (3D) models of human tumor invasion and angiogenesis. These tumor-host bioassay systems would allow analysis of discrete cellular and molecular events of tumor growth and progression in vitro. The Phase I specific goals are: 1. Develop and optimize HuBiogel assay systems using defined biomatrix formulations and 3D cell culture configurations and; 2. Demonstrate practical applications for monitoring key tumorigenesis events using multicellular tumor spheroid cocultures with fibroblasts or endothelial cells. In the second phase of this R&D project, functional studies of new bioassays will be expanded for validation with other human tumor models. The timely development of this clinically relevant model will positively impact cancer biology, drug discovery and therapeutic arenas. Commercial Importance & Significance: No acceptable commercial tumor model currently exists which utilizes a defined human biomatrix system. DSI will develop reusable and disposable 3D tumor invasion and angiogenesis bioassays. Sale of HuBiogel and pre-packed assay systems would have a significant world-wide market, both as a research and diagnostic tool.