Brain Mimetic Materials for Cancer Cell Migration Studies

该奖项是根据2009年美国复苏和再投资法案(Public Law 111-5)0854015温特资助的。本项目的研究目标是创建新的脑模拟和迁移模型，以探索细胞外基质(ECM)对胶质瘤细胞迁移的影响。模拟物由水凝胶组成；膨胀的、交联的、但不溶的聚合物网络，由透明质酸和蛋白多糖(例如，短链多糖和多聚糖)组成。模拟材料将被用来构建两个体外细胞迁移的三维模型：侵袭试验，它检查细胞从溶液到3D脑组织模拟物的迁移；以及界面分析，它检查细胞从一种成分的3D大脑模拟物到不同成分的大脑模拟物的迁移。这些模型不同于目前研究肿瘤细胞迁移的方法，因为它们(A)由自然出现在大脑中的材料组成，(B)是三维的，更接近于体内的条件。成果包括脑组织模拟材料、细胞迁移模型、细胞对两种脑组织模拟材料(即添加了Brivican的“癌症”脑和添加了Versican的“正常”脑)的细胞反应的初步分析、研究生和本科生水平的工程学学生教育，以及基于这项研究为当地科学博物馆COSI举办的走廊手推车展览。这项研究将提供新的工具，有可能改变对胶质瘤癌细胞迁移的理解。胶质瘤是大脑中支持细胞的肿瘤，是最致命的癌症之一，从确诊之日起平均存活10-30个月，每年影响22,500人。它们特别难治疗，因为它们具有极强的侵袭性，渗透到整个大脑。除了临床上的好处，这项工作还将加强研究基础设施，在工程部门和临床部门之间建立新的合作。研究成果将通过期刊出版物、会议报告以及与地区科学博物馆的互动向公众传播。研究生和本科生将参与这项研究，研究结果也将通过课堂材料传播。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0854015WinterThis research objective of this project is to create new brain mimetics and migration models to explore the effect of the extracellular matrix (ECM) on glioma cell migration. The mimetics consist of hydrogels; swollen, cross-linked, yet insoluble, polymer networks, composed of hyaluronic acid and proteoglycans (e.g., brevican and versican). Mimetic materials will be used to construct two three-dimensional models of in vitro cell migration: an invasion assay, which examines migration of cells from solution into a 3D brain tissue mimetic; and in interface assay, which examines migration of cells from a 3D brain mimetic of one composition into a brain mimetic of differing composition. These models differ from current methods of investigating tumor cell migration because they are (a) composed of materials that naturally occur in the brain, (b) are three-dimensional, more closely mimicking in vivo conditions. Deliverables include brain tissue mimetic materials, models of cell migration, preliminary analysis of cell response to two types of brain tissue mimetic materials (i.e., 'cancer' brain with added brevican, 'normal' brain with added versican), engineering student education at the graduate and undergraduate level, and a hallway cart exhibit based on this research for COSI, a local science museum.The research will provide new tools with the potential to transform understanding of glioma cancer cell migration. Gliomas, tumors of supporting cells in the brain, are among the most deadly cancers, with an average survival of 10-30 months from time of diagnosis, and affect 22,500 individuals/year. They are particularly difficult to treat because they are highly aggressive, infiltrating throughout the brain. In addition to clinical benefits, this work will enhance research infrastructure, creating new collaborations between engineering and clinical departments. Research results will be disseminated through journal publications, conference presentations, and also, to the general public, through interactions with an area science museum. Graduate and undergraduate students will participate in the research, and results will be disseminated through classroom materials as well.