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Application of Human Induced Pluripotent Stem Cell-Derived Cellular and Organoid Models for COVID-19 Research.

ABSTRACT: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread has caused the coronavirus disease 2019 (COVID-19) pandemics, which is a global public health crisis. Thus, there is an urgent need to establish biological models to study the pathology of SARS-CoV-2 infection, which not only involves respiratory failure, but also includes dysregulation of other organs and systems, including the brain, heart, liver, intestines, pancreas, kidneys, eyes, and so on. Cellular and organoid models derived from human induced pluripotent stem cells (iPSCs) are ideal tools for in vitro simulation of viral life cycles and drug screening to prevent the reemergence of coronavirus. These iPSC-derived models could recapitulate the functions and physiology of various human cell types and assemble the complex microenvironments similar with those in the human organs; therefore, they can improve the study efficiency of viral infection mechanisms, mimic the natural host-virus interaction, and be suited for long-term experiments. In this review, we focus on the application of in vitro iPSC-derived cellular and organoid models in COVID-19 studies.

SUBMITTER: Luo Y

PROVIDER: S-EPMC8450444 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSARS-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.MethodsWe 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.ResultsInfected 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.ConclusionsFindings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines.FundingThis work was supported by the National Institutes for Health (NIH) grants 1R01DK107585-01A1, 3R01DK107585-05S1 (to SD); R01-AI141630, CA100768 and CA160911 (to PG) and R01-AI 155696 (to PG, DS and SD); R00-CA151673 and R01-GM138385 (to DS), R01- HL32225 (to PT), UCOP-R00RG2642 (to SD and PG), UCOP-R01RG3780 (to P.G. and D.S) and a pilot award from the Sanford Stem Cell Clinical Center at UC San Diego Health (P.G, S.D, D.S). GDK was supported through The American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists. L.C.A's salary was supported in part by the VA San Diego Healthcare System. This manuscript includes data generated at the UC San Diego Institute of Genomic Medicine (IGC) using an Illumina NovaSeq 6000 that was purchased with funding from a National Institutes of Health SIG grant (#S10 OD026929).

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Application of Human Induced Pluripotent Stem Cell-Derived Cellular and Organoid Models for COVID-19 Research.

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