Tissue Engineered In Vitro Human Airway Models of Asthma and COPD

哮喘和慢性阻塞性肺病的体外人体气道组织工程模型

基本信息

批准号：
7272305
负责人：
PATRICK J HAYDEN
金额：
$ 21.55万
依托单位：
MATTEK CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7272305
关键词：
3-Dimensional Address Adherent Culture Affect Aftercare Air Alveolar Alveolar Cell Alveolus Animal Model Animals Applications Grants Autologous Biological Models Cell Communication Cell Separation Cells Chronic Chronic Bronchitis Chronic Obstructive Airway Disease Chronic Obstructive Asthma Coculture Techniques Collagen Complex Computer Systems Development Dendritic Cells Deposition Development Disease Electrical Resistance Epithelial Epithelial Cells Equipment and supply inventories Extracellular Matrix Feedback Fibroblasts Foundations Future Gel Gene Expression Genetic Goals Goblet Cells Growth Factor Histology Human Human Virus Hyperplasia In Vitro Individual Interferons Interleukin-12 Interleukin-13 Interleukin-4 Investigation Liquid substance Lung Lung diseases Lymphocyte Matrix Metalloproteinases Mediator of activation protein Membrane Mesenchymal Modeling Mucins Pathogenesis Pharmacologic Substance Phase Phase II Clinical Trials Production Pulmonary Emphysema Research Research Personnel Role Small Business Funding Mechanisms Small Business Innovation Research Grant Smooth Muscle Myocytes Source Specimen Squamous Metaplasia Testing Therapeutic Therapeutic Human Experimentation Therapeutic Intervention Tissue Engineering Tissue Model Tissues Viral Work airway epithelium base bronchial epithelium cell bank cell type chemokine cytokine eosinophil in vitro Model interest novel therapeutics pre-clinical reconstitution response tool

项目摘要

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.

描述（由申请人提供）：哮喘和慢性阻塞性肺病（COPD）是美国两种主要的慢性呼吸道疾病。然而，对于试图了解哮喘和慢性阻塞性肺病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，可靠的体外人体模型尚未广泛使用。本拨款提案的目标是通过开发商业上可用的组织工程体外人类哮喘和慢性阻塞性肺病模型来满足这一未满足的需求。这些模型将由分化良好的人气管/支气管上皮 3D 培养物以及与人气道间充质细胞共培养的人气道上皮组成。从患病组织中分离出的上皮细胞和间充质细胞将用于制作模型。在第一阶段作为模型生产来源而启动的细胞库将在第二阶段和未来几年进行扩展，以建立更大的细胞库存并在使用时补充细胞。哮喘和慢性阻塞性肺病的组织工程体外人体模型将提供动物模型无法提供的重要独特属性，包括解决人类个体差异和遗传因素的能力；确定人类病毒诱发哮喘和慢性阻塞性肺病恶化机制的方法；以及在临床前/动物前水平上开发更高通量、更经济的哮喘和慢性阻塞性肺病治疗方法。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慢性阻塞性肺病发病机制中的作用，以及开发和测试这些疾病的新治疗方法。本拨款提案的目标是开发商用组织工程体外人体哮喘和慢性阻塞性肺病模型。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分化良好的 3D 培养物组成。从患病组织中分离出的上皮细胞和间充质细胞将用于制作模型。即将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慢性阻塞性肺病发病机制中的作用，以及开发和测试这些疾病的新治疗方法。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

DOI：
10.1371/journal.pone.0118286
发表时间：
2015
期刊：
PloS one
影响因子：
3.7
作者：
Bai J;Smock SL;Jackson GR Jr;MacIsaac KD;Huang Y;Mankus C;Oldach J;Roberts B;Ma YL;Klappenbach JA;Crackower MA;Alves SE;Hayden PJ
通讯作者：
Hayden PJ