Cell Stem Cell
Volume 27, Issue 1, 2 July 2020, Pages 125-136.e7
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Short Article
A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids

https://doi.org/10.1016/j.stem.2020.06.015Get rights and content
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Highlights

  • A hPSC-derived cell and organoid platform is used to study SARS-CoV-2 tissue tropism

  • Human pancreatic alpha and beta cells are permissive to SARS-CoV-2 infection

  • Human hepatocyte and cholangiocyte organoids are permissive to SARS-CoV-2 infection

  • hPSC-derived cells/organoids show similar chemokine responses as COVID-19 tissues

Summary

SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.

Keywords

human pluripotent stem cells
SARS-CoV-2
pancreatic endocrine cells
alpha cells
beta cells
liver organoids

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17

These authors contributed equally

18

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