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Human pluripotent stem cell-based organoids and cell platforms for modelling SARS-CoV-2 infection and drug discovery
Alice Maria Giani1, Shuibing Chen1
1Department of Surgery, Weill Cornell Medicine, 1300 York Ave, New York, NY 10065, USA.
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.
Insights
Human stem cell models, including organoids, are vital for studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mechanisms and identifying potential COVID-19 treatments. These models help understand disease pathogenesis and cellular responses in vitro.
Area of Science:
- Stem cell biology
- Virology
- Infectious diseases
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, necessitates effective research models.
- Human pluripotent stem cell (hPSC)-based platforms are emerging as critical tools for studying viral infections.
- Understanding SARS-CoV-2 pathogenesis requires in vitro models that recapitulate human tissue responses.
Purpose of the Study:
- To provide an overview of human pluripotent stem cell-based platforms for SARS-CoV-2 research.
- To highlight the utility of these models in investigating infection mechanisms and cellular responses.
- To discuss the application of these platforms in drug discovery and understanding COVID-19 pathophysiology.
Main Methods:
- Review of existing literature on stem cell-based models for SARS-CoV-2 research.
- Description of monolayer cultures and organoid platforms derived from human pluripotent stem cells.
- Analysis of the strengths and limitations of these in vitro models.
Main Results:
- Human stem cell-derived monolayer cultures and organoids effectively model SARS-CoV-2 infection in various tissues in vitro.
- These platforms identify susceptible cell types and aid in understanding viral pathogenesis.
- Stem cell models have been instrumental in identifying potential drug candidates for COVID-19 treatment.
Conclusions:
- Human pluripotent stem cell-based models are versatile and crucial for advancing the understanding of SARS-CoV-2.
- These platforms facilitate research into infection mechanisms, cellular responses, and therapeutic strategies for COVID-19.
- While valuable, limitations exist in fully recapitulating the complex pathophysiology of COVID-19.
