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Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 bioRxiv 2021 ; ä (ä): ä Nephropedia Template TP
Tindle C; Fuller M; Fonseca A; Taheri S; Ibeawuchi SR; Beutler N; Katkar G; Claire A; Castillo V; Hernandez M; Russo H; Duran J; Crotty Alexander LE; Tipps A; Lin G; Thistlethwaite PA; Chattopadhyay R; Rogers TF; Sahoo D; Ghosh P; Das S
bioRxiv 2021[May]; ä (ä): ä PMID33106807show ga
SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection whereas distal alveolar differentiation (AT2-->AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19 which can be immediately utilized to investigate COVID-19 pathogenesis, and vet new therapies and vaccines.