Lung viral infection modelling in a bioengineered whole-organ.
Lung viral infection modelling in a bioengineered whole-organ.
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DOI：
10.1016/j.biomaterials.2023.122203
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发表时间：
2023-10
期刊：
影响因子：
14
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中科院分区：
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肺部感染是全球主要的死亡原因之一，而新冠肺炎的出现加剧了这种情况。病毒感染的临床前建模依赖于缺乏3D结构和肺细胞外基质背景的细胞培养。在这里，我们提出了一种基于生物反应器的全器官肺病毒感染模型。该生物反应器利用自动化系统实现了整个大鼠肺的高效脱细胞，并使用原代人支气管细胞实现了支架的再细胞。自动化允许在模拟呼吸的设置中动态培养呼吸道上皮细胞，从而使肺上皮细胞均匀分布在远端区域。在密封的生物反应器系统中，我们通过感染原代人类呼吸道上皮细胞并随后注射中性粒细胞来证明上皮化肺内的病毒感染的概念。此外，为了评估在这个模型中进行药物筛选的可能性，我们展示了广谱抗病毒药物雷米德韦的有效性。这一全器官规模的肺部感染模型代表了在3D环境下模拟人类细胞病毒感染的一步，为研究病原性感染早期阶段的机制和开发有效的呼吸道疾病治疗策略提供了强大的工具。
Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection within the epithelialized lung by infecting primary human airway epithelial cells and subsequently injecting neutrophils. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases.
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影响因子：
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作者：
Tsuchiya T;Mendez J;Calle EA;Hatachi G;Doi R;Zhao L;Suematsu T;Nagayasu T;Niklason LE
通讯作者：
Niklason LE
影响因子：
14
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影响因子：
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