Establishment of human distal lung organoids for SARS-CoV-2 infection

Protease inhibitor Camostat Mesyalte blocks wild type SARS-CoV-2 and D614G viral entry in human engineered miniature lungs

“…While various vaccines have shown drastic effects on preventing COVID-19 infection and reducing its severity, the discovery of effective novel forms of treatment of COVID-19 has lagged behind. To study this devastating disease and its pathophysiology, in vitro models mimicking human lung tissue including 3D cultured organoids [ [5] , [6] , [7] , [8] ], air-liquid interface cultured epithelium [ 11 , [27] , [28] , [29] ], and lung-on-a-chip [ [9] , [10] , [11] , [12] , [13] ] have provided valuable research platforms. However, none of these replicate the structure of human lungs, therefore limiting the ability to simulate and analyze critical events during and after COVID-19 infection, including the primary infection, disease progression and the related pathophysiology of airway cells [ 30 ].…”

“…To investigate how to intervene in this disease process and to inhibit various steps of the SARS-CoV-2 lifecycle, we need a universally available, affordable, scalable, and yet physiologically relevant platform simulating the human respiratory tract. Recently, several groups reported the application of human lung cells [ 3 , 4 ], organoids [ [5] , [6] , [7] , [8] ], and organ-on-a-chip microfluidic systems [ [9] , [10] , [11] , [12] , [13] ] for the study of SARS-CoV-2 infection and induced immune responses. However, the discrepancies between these platforms and native human lung make it hard to recapitulate the pathophysiological behavior of SARS-CoV-2 virus during infection.…”

In vitro high-content tissue models to address precision medicine challenges

“…These models have been suggested as a prominent platform to gain a fundamental understanding of viral infections such as COVID-19 ( Basanthakumar, 2021 ; de Melo et al, 2021 ; Deguchi et al, 2021 ; Harb et al, 2022 ; Kronemberger et al, 2021 ; Lv et al, 2021 ; Ramani et al, 2021 ; Sia et al, 2022 ; Sourimant et al, 2022 ; van der Vaart et al, 2021 ; Wang et al; Yu, 2021 ; Zech et al, 2021 ) and could be a good alternative to facilitate the development and discovery of new therapeutics and vaccines ( Clevers, 2020 ; Raimondi et al, 2020 ). To date, various types of organoid-enabled 3D models have been employed to study and understand SARS-CoV-2 infection such as the brain organoid ( Ramani et al, 2020 ), lung organoid ( Ekanger et al, 2022 ; Salahudeen et al, 2020 ; van der Vaart et al, 2021 ; Wang et al, 2021a ), intestine organoid ( Dickson, 2020 ), as well as liver ductal organoid and bile duct organoid ( Zhao et al, 2020a ) ( Fig. 3 ).…”

“…Scale bars are 50 μm. Reproduced with permission ( Wang et al, 2021a ). Copyright 2022, Springer Nature, Wang et al, Licensed under A Creative Commons Attribution License (CC BY).…”

“…Moreover, Wang and coauthors devised human distal lung organoids infected with SARS-CoV-2 to understand the serial cellular responses as a result from the infection through immunofluorescence staining ( Fig. 3 b) ( Wang et al, 2021a ). The authors demonstrated that their disclosed model could mimic the pathological changes in COVID-19 patients, and the study showed cellular responses such as a downregulation of keratinization, a metabolic switch from oxidative phosphorylation to glycolysis, decreased lysosomal function, and apoptosis, among others ( Wang et al, 2021a ).…”