In Vitro Lung Models and Their Application to Study SARS-CoV-2 Pathogenesis and Disease

Abstract

SARS-CoV-2 has spread across the globe with an astonishing velocity and lethality that has put scientist and pharmaceutical companies worldwide on the spot to develop novel treatment options and reliable vaccination for billions of people. To combat its associated disease COVID-19 and potentially newly emerging coronaviruses, numerous pre-clinical cell culture techniques have progressively been used, which allow the study of SARS-CoV-2 pathogenesis, basic replication mechanisms, and drug efficiency in the most authentic context. Hence, this review was designed to summarize and discuss currently used in vitro and ex vivo cell culture systems and will illustrate how these systems will help us to face the challenges imposed by the current SARS-CoV-2 pandemic.

Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals

“…The human respiratory tract is the primary route of SARS-CoV-2 infection [ 1 , 5 , 6 , 7 , 8 ]. During the past year, in vitro organotypic cell cultures of the human airway epithelium have been used extensively to help further our knowledge of SARS-CoV-2 biology and the host response to infection [ 9 ]. These include air–liquid interface (ALI) culture systems that support the differentiation of primary human bronchial epithelial cells (HBECs) into a mucociliary epithelium and alveosphere cultures of distal lung alveolar type 2 cells that mimic key aspects of the in vivo epithelium present in the upper airways and distal lung, respectively [ 5 , 6 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

Intracellular Life Cycle Kinetics of SARS-CoV-2 Predicted Using Mathematical Modelling

“…To progress further with the development of relevant multiscale mathematical models, all these cell types need to be characterized with respect to the SARS-CoV-2 life cycle. For reviews on experimental models which are developed to study SARS-CoV-2 replication in cultures of various target cells, we refer to [ 55 , 56 , 57 , 58 ].…”

Influenza viruses and coronaviruses: Knowns, unknowns, and common research challenges

“…The cell lines that are widely used in influenza and CoV research (e.g., MDCK, Vero-E6, and A549) bear very little resemblance to the human respiratory epithelium, which can compromise the relevance and applicability of the findings. The use of primary cells, induced human pluripotent stem cells, and 3D lung-on-a-chip or organoid cultures should be facilitated and developed, to provide more accurate models for the differentiated respiratory epithelium or the microanatomy of the lung [ 173 ]. Likewise, it is crucial to set up animal models that mimic more closely the physiopathology in human patients and can provide reliable information for fundamental research as well as preclinical testing of therapeutic and vaccine candidates [ 106 , 174 ].…”