Organoids: A New Model for SARS-CoV-2 Translational Research

Abstract

The 2019-novel coronavirus (SARS-CoV-2) pneumonia epidemic is a thorny public health problem faced by health officials and a major cause of concern for health professionals. However, the currently used immortalized cell lines and animal models, though easy to manipulate, can not thoroughly simulate real viral activity due to a lack of target cells, species isolation, and insufficient adequate tissues and organs for clinical research. Organoid that emerges as an effective model and time-saving approach can simulate the viral life cycle in vitro and explore a therapeutic target for antiviral drug development. The 3D tissue cultures contain patient-specific stem cells in vitro to mimic the complexity of real tissue within the 3D microstructure that has the same functionality as the tissue of interest. It avoids the problems such as the distortion of genetic markers and animal ethics of using 2D cultures for animal testing and can be employed in studies of specific-organ viral infections to fully understand the physiopathological mechanism of SARS-CoV-2 infection for vaccine research and development.

Application of Human Induced Pluripotent Stem Cell-Derived Cellular and Organoid Models for COVID-19 Research

“…In the above studies, single-cell RNA-seq has been employed to screen for cell types that are positive of the SARS-CoV-2 receptor ACE2 and effector protease TMPRSS2, and to illustrate the transcriptional alternations after viral infection ( Huang J. et al, 2020 ; Yang et al, 2020 ; Zang et al, 2020 ). Furthermore, the CRISPR system can be utilized to create genetically modified iPSC models for mechanism study of the candidate genetic factors ( Luo et al, 2015c , 2016 ; Gkogkou et al, 2020 ; Kim et al, 2020 ; Zang et al, 2020 ; Yu, 2021 ). For example, with a CRISPR-engineered iPSC model, researchers have demonstrated that the single-nucleotide polymorphism rs4702, which is a common genetic variant located in the 3′ UTR of the protease FURIN, influences the SARS-CoV-2 permissiveness of alveolar and neuronal cells ( Dobrindt et al, 2021 ).…”

Organoid and microfluidics-based platforms for drug screening in COVID-19

“… [47] , [51] , [52] In addition, organoids, to some extent, also enable assessment of drug diffusion and delivery, enhancing the predictability of drug screens in 3D compared with 2D cultures. [53] Hence, organoids could overcome challenges in preclinical drug screening in terms of safety, efficiency, and cost-effectiveness, as well as genotype–phenotype testing, with the aim of personalized and regenerative medicine. [51] , [54] …”

Recent Advances of COVID-19 Modeling Based on Regenerative Medicine

“…Organoid systems can provide a rapid platform for comparison of these strains and their susceptibility to vaccines and drugs (Mohammadi et al, 2021;van der Vaart et al, 2021). Modifying the organoids by using novel technologies like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein9 (CRISPR/Cas9) and biomaterials as well as combining different cell types can result in more applicable and reliable pre-clinical models (Yu, 2021).…”

“…Limbus was found to be the most susceptible part which exhibited a significant NF-κB mediated inflammatory response. However, it is not clear whether the inflammation is due to direct infection or the virus spreading to the eye through systemic infection ( Makovoz et al, 2020 ; Yu, 2021 ). Altogether, it seems that the eye is a route of infection; hence the organoids and monolayer cultures represent useful models of studying the SARS-CoV-2 mechanism of pathogenesis ( Ahmad Mulyadi Lai et al, 2021 ).…”

“…Besides, the current technology of organoids cannot manifest the communication between different organs and immunological responses in COVID-19 infection. In this context, animal models are more advantageous ( Yu, 2021 ). As one of the most necessary major phases in manufacturing biomedical products, the ideal animal models should be able to simulate the disease in humans and its manifestations as similar to humans as it is possible.…”