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. 2021 May:53:102207.
doi: 10.1016/j.scr.2021.102207. Epub 2021 Feb 20.

Human pluripotent stem cell-based organoids and cell platforms for modelling SARS-CoV-2 infection and drug discovery

Affiliations

Human pluripotent stem cell-based organoids and cell platforms for modelling SARS-CoV-2 infection and drug discovery

Alice Maria Giani et al. Stem Cell Res. 2021 May.

Abstract

The coronavirus disease 2019 (COVID-19) global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 200 countries and territories worldwide and resulted in more than 2.5 million deaths. In a pressing search for treatments and vaccines, research models based on human stem cells are emerging as crucial tools to investigate SARS-CoV-2 infection mechanisms and cellular responses across different tissues. Here, we provide an overview of the variety of human pluripotent stem cell-based platforms adopted in SARS-CoV-2 research, comprising monolayer cultures and organoids, which model the multitude of affected tissues in vitro. We highlight the strengths of these platforms, including their application to assess both the susceptible cell types and the pathogenesis of SARS-CoV-2. We describe their use to identify drug candidates for further investigation in addition to discussing their limitations in fully recapitulating COVID-19 pathophysiology. Overall, stem cell models are facilitating the understanding of SARS-CoV-2 and prove to be versatile platforms for studying infections.

Keywords: (6 MAX); COVID-19; Drug discovery; Organoid; Personalized medicine; SARS-CoV-2; Stem cells.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shuibing Chen reports financial support was provided by National Institute of Diabetes and Digestive and Kidney. Shuibing Chen reports financial support was provided by Bill and Melinda Gates Foundation.

Figures

Fig. 1
Fig. 1
hPSC-based Models of SARS-CoV-2 Infection. Schematic representation of the hPSC-based monolayer cultures and organoids used to date to study SARS-CoV-2 tropism and COVID-19 pathophysiology across different organs.
Fig. 2
Fig. 2
Applications of hPSC-based Models in COVID-19 research. Schematic illustration of how hPSC-based platforms are used to investigate the cell-type-specific susceptibility and response to SARS-CoV-2 infection as well as to identify new candidate treatments. Assays and applications are placed on different backgrounds. Yellow: common assays performed to date using hPSC-based platforms, Green: currently widespread applications of hPSC-based platforms, Light blue: potential future applications of hPSC-based platforms. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

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