Engineering an in vitro lung model for air pollutant deposition and toxicology

设计用于空气污染物沉积和毒理学的体外肺模型

• 批准号: 7148165
• 负责人: John Volckens
• 金额: $ 13.52万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-16 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148165
• 关键词: aerosols; air pollution; air pollution control; disease /disorder model; disease /disorder prevention /control; environmental exposure; environmental health; environmental toxicology; lung disorder; mass screening; model design /development; particle; pollution related respiratory disorder; respiratory disorder diagnosis; respiratory epithelium; tissue /cell culture

DESCRIPTION (provided by applicant): The candidate's overall career goal is to become a leading, independent researcher in the field of air pollution and air pollution effects on public health. Career objectives related to this grant are to: a) enhance the candidate's knowledge of pulmonary biochemistry and physiology, b) develop technical expertise in cellular toxicology, and c) develop an independent research program that integrates the fields of mechanistic toxicology with air pollution physics and exposure assessment. The long term goal of this research is to establish mechanistic, dose-response relationships between inhaled air pollutants and lung disease. Merging the fields of in vitro toxicology and exposure assessment is a necessary step in realizing this goal. Therefore, the immediate objective is to develop a realistic, physiological model for air pollutant deposition in vitro. The investigator's model will accomplish this task by approximating particle size-specific deposition patterns of particulate aerosols to pulmonary epithelial cells housed within a state-of-the-art in vitro lung model. This model will be developed, calibrated, and finally validated against the existing state-of-the-art model. In vitro toxicology can be employed as a relatively low-cost, rapid screening method for elucidating these mechanisms across many cell types. Establishing a link between exposure and health effect 1) provides a means for further innovations in the prevention and treatment of pulmonary disease, specifically allowing for more targeted (and resource-intensive) in vivo experimentation to follow from in vitro screening tests, 2) allows for intervention and control strategies targeted to reduce specific toxic components of ambient air pollution, and 3) helps provide the necessary information for regulating agencies to set more protective, health-based standards.

描述（由申请人提供）： 候选人的整体职业目标是成为空气污染和空气污染对公共卫生影响的领先，独立的研究人员。与该赠款相关的职业目标是：a）增强候选人对肺生物化学和生理学的了解，b）在细胞毒理学方面发展技术专长，c）制定一个独立的研究计划，将机​​械毒理学的领域与空气污染物理学和暴露物理学和暴露评估相结合。这项研究的长期目标是在吸入空气污染物和肺部疾病之间建立机械性的剂量反应关系。 合并体外毒理学和暴露评估的领域是实现这一目标的必要步骤。因此，直接目标是开发一个现实的生理模型，用于体外空气污染物沉积。 研究者的模型将通过将颗粒气溶胶的粒度特异性沉积模式近似于最先进的体外肺模型内的肺上皮细胞。该模型将被开发，校准，并最终针对现有的最新模型进行验证。 体外毒理学可以用作一种相对低成本的快速筛查方法，以阐明许多细胞类型的这些机制。建立暴露与健康效应之间的联系1）为预防和治疗肺部疾病的进一步创新提供了一种手段，特别允许在体内实验中进行更多有针对性的（和资源密集的）实验性（资源密集型），从体外筛查测试中进行遵循，2）允许干预和控制策略，以减少对环境空气污染的影响，以便为环境污染提供更多的污染，并有助于建立污染的特定毒性，并有助于建立污染的信息，并有助于建立污染的信息，并有助于建立污染的信息。