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COVID-19: 3D Bioprinted Tissue Models for Respiratory Viruses

COVID-19：呼吸道病毒的 3D 生物打印组织模型

基本信息

批准号：
10510408
负责人：
Marc Ferrer-Alegre
金额：
$ 159.49万
依托单位：
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10510408
关键词：
2019-nCoV 3-Dimensional Address Air Alveolar Alveolar Cell Antiviral Agents Biological Assay Biomedical Research Blood Vessels Brain COVID-19 COVID-19 patient COVID-19 pneumonia COVID-19 treatment Cardiac Cells Clinical Collaborations Communities Community Developments Coronavirus DNA Sequencing Facility Data Analyses Disease Drug Screening Epithelial Epithelial Cells Event Funding Human Immune In Vitro Infection Intestines Kidney Laboratories Liquid substance Lung Microfluidics Modeling National Institute of Allergy and Infectious Disease National Institute of Child Health and Human Development Pathology Pennsylvania Permeability Pharmaceutical Preparations Pharmacology Physiological Positioning Attribute Protocols documentation Public Health Research Activity Research Institute Research Support SARS-CoV-2 infection SARS-CoV-2 inhibitor Scientist Societies Structure of parenchyma of lung System Testing Texas Therapeutic Therapeutic Intervention Tissue Model Tissues Tracheobronchial Translational Research United States National Institutes of Health Universities Vaccines Variant Viral Viral Respiratory Tract Infection Virus Virus Diseases airway epithelium atypical pneumonia betacoronavirus biofabrication bioprinting clinical efficacy drug development drug repurposing in vitro Assay in vivo influenzavirus novel pandemic disease parainfluenza virus programs research and development respiratory respiratory pathogen respiratory virus response screening therapeutic development thrombotic

项目摘要

We have established protocols for culturing primary human small airway epithelial cells and alveolar cells in a transwell air-liquid-interface (ALI) model. Tissue biofabrication has been optimized in a 96-well plate format, including the formation of a microvessel network. We are positioning these lung tissue models platforms for testing infectivity of viral variants and anti-viral therapeutics for programs at NCATS, NIH and the broader research and drug development community. We have also developed a vascularized perfused lung epithelial tissue model in a high throughput microfluidics platform to assess of viral infection vasculature leakiness and permeability and thrombotic events seen in COVID-19 patients. We have characterized extensively the infectivity of the MatTek's tracheobronchial and alveolar cultures with SARS-CoV2 and IAV. We have also assessed the anti-viral effects of a focused number of compounds identified from HTS. In collaboration with Sara Cherry at the University of Pennsylvania, we have identified that Pharmacological activation of STING blocks SARS-CoV-2 infection. We continue to explore additional relevant therapeutic opportunities from drug screens at UPenn. We are working with the NICHD Sequencing Core lab and scientists at the Texas Biomedical Research Institute to implement scRNAseq studies on tracheobronchial and alveolar lung tissue models infected with IAV and SARS-CoV2. Data analysis is currently on-going.

我们已经建立了在transwell气液界面（ALI）模型中培养原代人小气道上皮细胞和肺泡细胞的方案。组织生物制造已在96孔板格式中进行了优化，包括微血管网络的形成。我们正在为NCATS、NIH和更广泛的研究和药物开发社区的项目定位这些肺组织模型平台，用于测试病毒变体的传染性和抗病毒治疗。