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

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。组织生物制造以96孔板的形式进行了优化，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疗法。 我们还在高通量微流体平台上建立了血管灌流肺上皮组织模型，以评估新冠肺炎患者中出现的病毒感染、血管渗漏和通透性以及血栓事件。 我们已经广泛地用SARS-CoV2和IAV表征了Mattek的气管、支气管和肺泡培养的传染性。我们还评估了从HTS中鉴定的一些重点化合物的抗病毒效果。 与宾夕法尼亚大学的Sara Cherry合作，我们已经确定了STING的药理激活可以阻止SARS-CoV-2感染。我们继续从宾夕法尼亚大学的药物筛选中探索更多相关的治疗机会。 我们正在与NICHD测序核心实验室和德克萨斯生物医学研究所的科学家合作，对感染IAV和SARS-CoV2的气管、支气管和肺泡组织模型进行scRNAseq研究。目前正在进行数据分析。

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.