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：
10907368
负责人：
Marc Ferrer
金额：
$ 10.18万
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/10907368
关键词：
2019-nCoV 3-Dimensional Address Air Alveolar Alveolar Cell Antiviral Agents Antiviral Therapy Area Biological Assay Brain COVID-19 COVID-19 patient COVID-19 pneumonia COVID-19 treatment Cells Clinical Communities Community Developments Coronavirus Disease Epithelial Cells Epithelium Event Hepatocyte Human Immune Infection Intestines Laboratories Liquid substance Liver Lung Microfluidics Modeling National Center for Advancing Translational Sciences Neurons Pathology Perfusion Permeability Pharmaceutical Preparations Physiological Positioning Attribute Protocols documentation Public Health Research Activity Research Support SARS-CoV-2 infection Societies Structure of parenchyma of lung System Testing Therapeutic Intervention Tissue Model Tissues Tracheobronchial Translational Research United States National Institutes of Health Vaccines Variant Vascularization Viral Viral Physiology Virus Virus Diseases airway epithelium atypical pneumonia betacoronavirus biofabrication bioprinting clinical efficacy drug development drug repurposing in vitro Assay influenzavirus neural novel pandemic disease parainfluenza virus programs research and development respiratory respiratory virus response 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 are assessing infectivity of intestine tissues (Mattek) with SARS-CoV2, including studies on long term persistence. We have demonstrated that neural spheroids are infected by brain tropic viruses and shown that infection modulates the neuronal activity of these brain models. We have demonstrated that hepatic cell spheroids are infected by viruses and shown that infection modulates the activity of these liver models.

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。我们正在定位这些肺组织模型平台，用于测试病毒变异体的感染性和 NCATS、NIH 以及更广泛的研究和药物开发社区的抗病毒疗法。我们还在高通量微流体平台中开发了血管化灌注肺上皮组织模型，以评估病毒感染脉管系统渗漏性和渗透性以及 COVID-19 患者中观察到的血栓事件。我们正在评估 SARS-CoV2 肠道组织 (Mattek) 的感染性，包括长期持续性的研究。我们已经证明神经球体被脑热带病毒感染，并表明感染调节这些大脑模型的神经元活动。我们已经证明肝细胞球体被病毒感染，并表明感染调节这些肝脏模型的活性。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection.

嘧啶生物合成抑制剂与核苷类似物协同作用，阻断 SARS-CoV-2 感染。

DOI：
10.1101/2021.06.24.449811
发表时间：
2021
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Schultz,DavidC;Johnson,RobertM;Ayyanathan,Kasirajan;Miller,Jesse;Whig,Kanupriya;Kamalia,Brinda;Dittmar,Mark;Weston,Stuart;Hammond,HollyL;Dillen,Carly;Castellana,Lauren;Lee,JaeSeung;Li,Minghua;Lee,Emily;Constant,Samuel;Fer
通讯作者：
Fer

A humanized nanobody phage display library yields potent binders of SARS CoV-2 spike.