Development of human-derived, three-dimensional respiratory epithelial tissue constructs with perfusable microvasculature on a high-throughput microfluidics screening platform.
Development of human-derived, three-dimensional respiratory epithelial tissue constructs with perfusable microvasculature on a high-throughput microfluidics screening platform.
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DOI：
10.1088/1758-5090/ac32a5
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发表时间：
2022-02-14
期刊：
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
COVID-19大流行凸显了对基于人类呼吸道的检测平台的需求，以有效发现和开发抗病毒药物和疾病调节疗法。下呼吸道的生理相关组织模型，包括呼吸性细支气管和肺泡囊，是高度关注的，因为它们是严重SARS-CoV-2感染的主要部位，并且在COVID-19的终末期受影响最大。目前用于研究呼吸道病毒感染的上皮肺模型包括在空气-液体界面处的肺上皮细胞与成纤维细胞和内皮细胞，但此类模型不具有可灌注的微血管网络来研究病毒感染性和病毒感染诱导的血栓形成事件。使用高通量，64芯片微流控板为基础的平台，我们已经开发了两种新的血管化，下呼吸道多芯片模型的肺泡和小气道。两种模型均包括由人原代微血管内皮细胞、成纤维细胞和周细胞组成的可灌注微血管网络。已建立的生物制造方案还使得能够在血管化组织床顶部的气液界面处形成分化的肺上皮层。我们使用荧光显微镜、流式细胞术和电阻测量验证了血管化肺组织模型的生理相关细胞组成、结构和灌注。在高通量检测平台上的这些血管化的、可灌注的微流体肺组织将能够开发用于研究调查和药物发现的呼吸道病毒感染和疾病模型。
The COVID-19 pandemic has highlighted the need for human respiratory tract-based assay platforms for efficient discovery and development of antivirals and disease-modulating therapeutics. Physiologically relevant tissue models of the lower respiratory tract, including the respiratory bronchioles and the alveolar sacs, are of high interest because they are the primary site of severe SARS-CoV-2 infection and are most affected during the terminal stage of COVID-19. Current epithelial lung models used to study respiratory viral infections include lung epithelial cells at the air-liquid interface with fibroblasts and endothelial cells, but such models do not have a perfusable microvascular network to investigate both viral infectivity and viral infection-induced thrombotic events. Using a high throughput, 64-chip microfluidic plate-based platform, we have developed two novel vascularized, lower respiratory tract multi-chip models for the alveoli and the small airway. Both models include a perfusable microvascular network consisting of human primary microvascular endothelial cells, fibroblasts and pericytes. The established biofabrication protocols also enable the formation of differentiated lung epithelial layers at the air-liquid interface on top of the vascularized tissue bed. We validated the physiologically relevant cellular composition, architecture and perfusion of the vascularized lung tissue models using fluorescence microscopy, flow cytometry, and electrical resistance measurements. These vascularized, perfusable microfluidic lung tissue on high throughput assay platforms will enable the development of respiratory viral infection and disease models for research investigation and drug discovery.
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DOI：
10.1016/j.ejpb.2010.10.014
发表时间：
2011-04-01
影响因子：
4.9
作者：
Lehmann, Andrea D.;Daum, Nicole;Rothen-Rutishauser, Barbara M.
通讯作者：
Rothen-Rutishauser, Barbara M.
影响因子：
4.6
作者：
Chen F;Zhang Y;Sucgang R;Ramani S;Corry D;Kheradmand F;Creighton CJ
通讯作者：
Creighton CJ
影响因子：
4.6
作者：
Cozens D;Grahame E;Sutherland E;Taylor G;Berry CC;Davies RL
通讯作者：
Davies RL
DOI：
10.1073/pnas.1434429100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Chi, JT;Chang, HY;Brown, PO
通讯作者：
Brown, PO
影响因子：
17.1
作者：
Barosova, Hana;Maione, Anna G.;Rothen-Rutishauser, Barbara
通讯作者：
Rothen-Rutishauser, Barbara