A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Academic Article uri icon

Overview

abstract

  • 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.

authors

publication date

  • June 19, 2020

Research

keywords

  • Betacoronavirus
  • Coronavirus Infections
  • Induced Pluripotent Stem Cells
  • Models, Biological
  • Organoids
  • Pneumonia, Viral
  • Tropism

Identity

PubMed Central ID

  • PMC7303620

Scopus Document Identifier

  • 85086786731

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2020.06.015

PubMed ID

  • 32579880

Additional Document Info

volume

  • 27

issue

  • 1