Tissue Engineered In Vitro Human Airway Models of Asthma and COPD

描述（由申请人提供）：哮喘和慢性阻塞性肺疾病（COPD）是美国两种主要的慢性呼吸道疾病。然而，可靠的体外人体模型对于试图了解哮喘和COPD发病机制并开发这些疾病的治疗干预措施的药物研究人员来说并不广泛可用。本基金的目标是通过开发商业化的组织工程体外哮喘和COPD人体模型来满足这一未满足的需求。这些模型将由人气管/支气管上皮以及与人气道间充质细胞共培养的人气道上皮的分化良好的3-D培养物组成。从患病组织分离的上皮细胞和间充质细胞将用于产生模型。在第I阶段作为模型生产来源启动的细胞库将在第II阶段和未来几年扩大，以建立更大的细胞库存并在使用时补充细胞。用于哮喘和COPD的组织工程体外人类模型将提供动物模型无法提供的重要独特属性，包括解决人类个体变异性和遗传因素的能力;确定哮喘和COPD恶化的人类病毒诱发机制的方法;以及在临床前/动物前水平上开发哮喘和COPD治疗的更高通量、经济的方法。这些模型将为药物研究人员提供重要的新工具，用于研究气道上皮和间充质细胞在哮喘和COPD发病机制中的作用，以及开发和测试这些疾病的新治疗方法。本项目的目标是开发商业化的组织工程体外哮喘和慢性阻塞性肺病人体模型。这些模型将由气管/支气管上皮以及与气道间充质细胞共培养的气道上皮的良好分化的3-D培养物组成。从患病组织分离的上皮细胞和间充质细胞将用于产生模型。待开发的模型将为药物研究人员提供重要工具，用于研究气道上皮和间充质细胞在哮喘和COPD发病机制中的作用，以及开发和测试这些疾病的新治疗方法。

DESCRIPTION (provided by applicant): Asthma and chronic obstructive pulmonary disease (COPD) are the two leading chronic respiratory diseases in the US. However, reliable in vitro human models are not widely available to pharmaceutical researchers who are attempting to understand asthma and COPD pathogenesis and develop therapeutic interventions for these diseases. The goal of the present grant proposal is to fulfill this unmet need by developing commercially available tissue engineered in vitro human models of asthma and COPD. These models will consist of well-differentiated 3-D cultures of human tracheal/bronchial epithelium as well as human airway epithelium co-cultured with human airway mesenchymal cells. Epithelial and mesenchymal cells isolated from diseased tissues will be utilized to produce the models. A cell bank initiated as a source for model production during Phase I will be expanded during Phase II and in future years, to build a larger inventory of cells and to replenish cells as they are utilized. Tissue engineered in vitro human models for asthma and COPD will provide important unique attributes that animal models cannot provide, including the ability to address human individual variability and genetic factors; a means to determine mechanisms of human virus elicitation of asthma and COPD exacerbations; and a higher throughput, economical means of asthma and COPD therapeutic development at the preclinical/pre-animal level. These models will provide pharmaceutical researchers important new tools for investigating the role of airway epithelium and mesenchymal cells in asthma and COPD pathogenesis and development and testing of new therapeutic treatments for these diseases. The goal of the present grant proposal is to develop commercially available tissue engineered in vitro human models of asthma and COPD. These models will consist of well-differentiated 3-D cultures of tracheal/bronchial epithelium as well as airway epithelium co-cultured with airway mesenchymal cells. Epithelial and mesenchymal cells isolated from diseased tissues will be utilized to produce the models. The models to be developed will provide pharmaceutical researchers important tools for investigating the role of airway epithelium and mesenchymal cells in asthma and COPD pathogenesis and development and testing of new therapeutic treatments for these diseases.