Human induced pluripotent stem cells as a tool for disease modeling and drug screening for COVID-19

Nolasco, Patricia; Borsoi, Juliana; Moraes, Carolina Borsoi; Freitas-Junior, Lucio H.; Pereira, Lygia Veiga

doi:10.1590/1678-4685-GMB-2020-0198

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Genetics and Molecular Biology

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Articles • Genet. Mol. Biol. 44 (1 Suppl 1) • 2021 • https://doi.org/10.1590/1678-4685-GMB-2020-0198 copy

Human induced pluripotent stem cells as a tool for disease modeling and drug screening for COVID-19

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The emergence of the new corona virus (SARS-CoV-2) and the resulting COVID-19 pandemic requires fast development of novel prevention and therapeutic strategies. These rely on understanding the biology of the virus and its interaction with the host, and on agnostic phenotypic screening for compounds that prevent viral infection. In vitro screenings of compounds are usually performed in human or animal-derived tumor or immortalized cell lines due to their ease of culturing. However, these platforms may not represent the tissues affected by the disease in vivo, and therefore better models are needed to validate and expedite drug development, especially in face of the COVID-19 pandemic. In this scenario, human induced pluripotent stem cells (hiPSCs) are a powerful research tool due to their ability to generate normal differentiated cell types relevant for the disease. Here we discuss the different ways hiPSCs can contribute to COVID-19 related research, including modeling the disease in vitro and serving as a platform for drug screening.

Keywords:
Stem cell differentiation; COVID-19; drug screening; Brazil; human pluripotent stem cells

Model	Advantages	Disadvantages
hiPSC-derived cells	Human model, patient (genotype)-specific, suitable for gene editing	Labor/time consuming and higher cost culture
	Can generate multiple relevant cell-types with same genetic background	Some differentiated cell types with fetal phenotype
	Increased complexity can be achieved with co-culture and organoids	Possible variations among batches of differentiations
Human cancer/ immortalized lines	Easy to keep in culture and maintain	Fail to represent or mimic the tissues affected by the disease in vivo
Human cancer/ immortalized lines	Passage number is not a concern	Carry tumor-associated mutations, such as P53 mutations; some cell lines have mutations in genes controlling the innate immune response
Transgenic mice	Complete organism able to show systemic disease	Distinct from human biology and unlikely to capture key aspects of some diseases
Transgenic mice	Can be engineered to express molecules of interest	Use increasingly discouraged for ethical reasons

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E-mail: editor@gmb.org.br

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[1] Send correspondence to
Patricia Nolasco. Universidade de São Paulo, Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, Laboratório Nacional de Células-tronco Embrionárias (LaNCE), 05508-090, São Paulo, SP, Brazil. E-mail: patty_ns8@hotmail.com.