iPSCs: a tool to investigate SARS-CoV-2

iPSC-derivatives are key for physiologically relevant cell models 

Since the Coronavirus (SARS-CoV-2) pandemic began, many efforts have been made to investigate the biology of the virus and its interaction with the host.

In this scenario, human induced pluripotent stem cells (iPSCs) represent a powerful tool due to their ability to differentiate into any cell type from all three germ layers. iPSCs have been used to recreate human model systems, that can recapitulate disease pathogenesis or evaluate the tissue tropism of the Coronavirus.

For instance, researchers have optimised a protocol for obtaining alveolar epithelial type 2 cells (AT2s) from iPSCs [1, 2]. The AT2 cells are a significant component of the epithelium of the distal lung region. If infected with SARS-CoV-2, this leads to the patient developing severe pneumonia symptoms which is frequently observed in COVID-19 patients. This model has been used to elucidate a few key cell mechanisms in response to the virus infection and is a promising candidate for drug screening [1].

As widely reported, COVID-19 is also characterised by cardiac complications. iPSC-derived cardiomyocytes have been used to investigate the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2, revealing some transcriptomic and morphological signatures of damage in cardiomyocytes [3-5].

Clinical evidence also shows that COVID-19 might cause systemic inflammation, including in Central Nervous System (CNS) disorders. Therefore, several studies have focused on this using iPSCs-derived platforms. For instance, Kase and Okano investigated SARS-CoV-2 infection-ACE2-CCN1 axis in CNS disorders using iPSC-derived neural stem/progenitor cells and young neurons as models [6]. Moreover, iPSC-derived 3D-organoids of the cerebral cortex, hippocampus, hypothalamus, and midbrain have been used for mimicking and characterising the response to the infection in different regions of the brain [7].

Furthermore, iPSC-derived organoids have been used for modelling SARS-CoV-2 infection in a range of more organs, including the kidney, intestine, lung, liver and blood vessels [8-11].

The advent of iPSCs have changed the way to study host-virus interactions. The ability to generate the cell types of interest from iPSC lines to model viral infections in different tissues in vitro is extremely powerful. Moreover, iPSC-derived organoids which recapitulate multicellular systems are even more suitable models to investigate host-virus interactions and for screening drugs.  

ECACC distributes iPSCs through both the EBISC and HIPSCI collections which give researchers a wide choice of over 1,500 iPSC lines generated from a wide range of donors representing either >30 specific disease backgrounds or healthy normal donors.

References 

1. Huang, J., et al., SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response. Cell Stem Cell, 2020. 27(6): p. 962-973.e7.

2. Abo, K.M., et al., Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors. bioRxiv : the preprint server for biology, 2020: p. 2020.06.03.132639.

3. Sharma, A., et al., Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection. bioRxiv, 2020.

4. Kwon, Y., et al., Detection of viral RNA fragments in human iPSC cardiomyocytes following treatment with extracellular vesicles from SARS-CoV-2 coding sequence overexpressing lung epithelial cells. Stem Cell Res Ther, 2020. 11(1): p. 514.

5. Pérez-Bermejo, J.A., et al., SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients. 2020: p. 2020.08.25.265561.

6. Kase, Y. and H. Okano, Expression of ACE2 and a viral virulence-regulating factor CCN family member 1 in human iPSC-derived neural cells: implications for COVID-19-related CNS disorders. Inflammation and Regeneration, 2020. 40(1): p. 32.

7. Jacob, F., et al., Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium. Cell Stem Cell, 2020. 27(6): p. 937-950.e9.

8. Monteil, V., et al., Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell, 2020. 181(4): p. 905-913.e7.

9. Zhou, H., et al., A potential ex vivo infection model of human induced pluripotent stem cell-3D organoids beyond coronavirus disease 2019. Histol Histopathol, 2020. 35(10): p. 1077-1082.

10. Yang, L., et al., A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell, 2020. 27(1): p. 125-136.e7.

11. Lamers, M.M., et al., SARS-CoV-2 productively infects human gut enterocytes. Science, 2020. 369(6499): p. 50-54.

Written by Rosa Loffredo, January 2021