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Genetically modifed tissue engineered in vitro human models

转基因组织工程体外人体模型

基本信息

批准号：
7611928
负责人：
PATRICK J HAYDEN
金额：
$ 22.12万
依托单位：
MATTEK CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-15 至 2011-02-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7611928
关键词：
3-Dimensional Adherent Culture Apical Apoptosis Arts Asthma Basic Science Biological Models Breathing Bulla Carcinogenesis Mechanism Cell Culture Techniques Cell Line Cell physiology Cells Chronic Chronic Obstructive Airway Disease Cicatrix Client Coculture Techniques Contracts Cornea Cosmetics Cryopreserved Cell Cystic Fibrosis Transmembrane Conductance Regulator DNA DNA Maintenance DNA Repair Enzymes Defensins Dendritic Cells Dermal Detection Development Dimensions Disease Drug Industry Drug Interactions Ecdysone Environment Enzyme-Linked Immunosorbent Assay Enzymes Epithelial Epithelial Cells Equipment and supply inventories Feedback Fibroblasts Fibrosis Funding Future GADD45 Gene Activation Gene Expression Gene-Modified Genes Genetic Genome Genomics Gingiva Goals Green Fluorescent Proteins Health Household Products Human Human Genome Hydrogen Peroxide IL8 gene In Vitro Industry Inflammation Interstitial Collagenase Knock-out Laboratory Research Lac Repressors Lipids Lung Maintenance Malignant Neoplasms Matrix Metalloproteinases Mesenchymal Messenger RNA Methodology Methods Modeling Modification Monitor Mucins Natural Immunity Normal Cell Organ Oxidative Stress Pharmaceutical Preparations Pharmacologic Substance Phase Phase II Clinical Trials Play Process Production Proteins Protocols documentation RNA Interference Regulation Reporter Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role Signal Pathway Signal Transduction Skin Staging Stratum corneum Stromal Cells Structure Surface Suspension Culture System T-Lymphocyte TP53 gene Techniques Technology Tetracyclines Therapeutic Intervention Tissue Engineering Tissue Model Tissues Undifferentiated United States National Institutes of Health Vagina Validation Wound Healing airway epithelium airway remodeling base cell type crosslink cytokine cytotoxicity drug metabolism environmental agent functional genomics gene function genotoxicity human disease human tissue immortalized cell in vitro Model in vivo interest keratinocyte knockout gene model development monolayer novel novel therapeutics overexpression pathogen protein expression public health relevance research study response small hairpin RNA tool

项目摘要

DESCRIPTION (provided by applicant): The goal of the current proposal is to apply state of the art gene modification technology including lentiviral delivery systems and RNA interference technology to commercially available tissue engineered human in vitro models. These models will consist of differentiated 3-D epidermal cultures and tracheal/bronchial epithelial cultures, as well as epidermal and airway epithelia co-cultured with mesenchymal cells. In Phase I research, the technology will be used to produce 3 types of genetically modified tissue engineered culture products: 1) stable addition of a functional gene, 2) stable silencing of a gene, and 3) stable introduction of a reporter for detection of gene activation. During Phase II, the techniques will be applied to additional tissue engineered human in vitro models, and the inventory of available gene modified products will be expanded. These proposed commercially available in vitro model systems will provide researchers in the pharmaceutical industry and academic research laboratories a readily available means for studying the functional genomics of nearly any gene in human epithelial cells, as well as crosstalk between epithelial and stromal cells in the differentiated organotypic state. Use of these models will aid in identification and validation of targets for development of novel therapeutics for treatment of human skin and airway epithelial diseases including cancers, chronic wounds, blistering diseases, scarring, and airway remodeling associated with asthma and COPD. Public Health Relevance: The gene modified tissue engineered models to be produced by the current project will provide researchers in the pharmaceutical industry and academic research laboratories a readily available means for studying the functional genomics of nearly any gene in human epithelial cells, as well as crosstalk between epithelial and stromal cells in the differentiated organotypic state. The models will be utilized to identify and validate targets for the development of novel therapeutics for treatment of human skin and airway epithelial diseases including cancers, chronic wounds, blistering diseases, scarring, and airway remodeling associated with asthma and COPD.

描述(申请人提供)：当前提案的目标是将包括慢病毒递送系统和RNA干扰技术在内的最先进的基因修饰技术应用于商业上可获得的组织工程化人体体外模型。这些模型将包括分化的3-D表皮培养物和气管/支气管上皮培养物，以及与间充质细胞共培养的表皮和呼吸道上皮细胞。在第一阶段的研究中，该技术将用于生产3种类型的转基因组织工程培养产品：1)稳定添加功能基因，2)稳定沉默基因，3)稳定引入检测基因激活的报告。在第二阶段，这些技术将应用于更多的组织工程化人体体外模型，并将扩大可用基因修饰产品的库存。这些商业化的体外模型系统将为制药业和学术研究实验室的研究人员提供一种现成的手段，用于研究人类上皮细胞中几乎任何基因的功能基因组学，以及分化器官型状态的上皮细胞和基质细胞之间的串扰。这些模型的使用将有助于确定和验证用于治疗人类皮肤和呼吸道上皮疾病的新疗法的开发目标，这些疾病包括癌症、慢性伤口、起泡疾病、疤痕形成以及与哮喘和慢性阻塞性肺病相关的气道重塑。公共卫生相关性：本项目将生产的基因修饰组织工程模型将为制药业和学术研究实验室的研究人员提供一种现成的手段，用于研究人类上皮细胞中几乎任何基因的功能基因组学，以及上皮细胞和基质细胞在分化器官类型状态下的串扰。这些模型将用于确定和验证用于治疗人类皮肤和呼吸道上皮疾病的新疗法的开发目标，这些疾病包括癌症、慢性伤口、水泡性疾病、疤痕形成以及与哮喘和慢性阻塞性肺病相关的呼吸道重塑。