TABLE 1.
Pros and cons of stem cell and organoid models of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).
| Type of model | Pros | Cons | References | |
| Stem cell models | MSC-based models | - Lower cost in contrast to lung organoid models | - Various differentiation capacity of stem cells from different donors - variation in the number of infected cells in each set of cultures - Limited sample size due to the challenges and costs of obtaining human tissue - Lack of inflammatory cells in the cultures - Offering only short-term culture capabilities in contrast to the stability and indefinite growing capabilities of organoid models | Purkayastha et al., 2020; Chugh et al., 2021 |
| IPSC-derived models | - Generating various differentiated cells with same genetic background -Mimicking the biology of host-virus interaction - Patient (genotype)-specific - Suitable for gene editing - The susceptibility to become more complex via co-culturing - Easy to keep in culture and maintain | - Labor/time consuming and higher cost culture - Possible variations among paths of differentiations - Some limitations in representing the exact in vivo manifestation of infected tissues | Nolasco et al., 2020; Chugh et al., 2021 | |
| Organoid models | Brain | - Allowing the scientist to explore neurotoxic effect of COVID-19 - A suitable platform to study the antiviral effects of anti COVID-19 drugs through preserving BBB from viral damage | -Absence of vascularization as in human brain - Requiring modification for making long-term observation possible | Chugh et al., 2021 |
| Gut | - Containing all proliferative and differentiated cell types of the in vivo epithelium - Reflecting the high susceptibility of gastrointestinal system to be infected in vivo, by representing the high rate of enterocytes infection as the most common cell type pf intestinal system. | - Weakness in showing the patient’s defense mechanisms against digestive system infection during COVID-19 (intestinal flora and lymphatic system) | Lamers et al., 2020; Yu, 2021 | |
| Kidney | - Effectively representing COVID-19 associated AKI - Showing the efficacy of combination therapy using Remdesivir with human recombinant soluble ACE2 in reducing virus entry and replication. | - Cannot mimic the exact features of native renal tissue | Chugh et al., 2021 | |
| Cardiovascular system | - Suitable for exploring the efficacy of new drug candidates in reversing cardio-toxic effects of the virus - Appropriate for validating the potential role of specific genetic variants in COVID-19 pathology | - The impossibility of mimicking arrhythmia and myocardial infarction - The need for careful adjusting of drug doses because of higher drug levels in the organoid in comparison to human blood due to the absence of metabolic organs in the cardiovascular organoids | Yiangou et al., 2020; Yu, 2021 | |
| Lung | - Allowing efficient viral replication - Suitable for exploring interactions between human cells and viruses and the response of lung stem cells to SARS-CoV-2 - Can be used to test drugs targeting a wide range of viruses | - The absence of stroma and immune cells - The absence of a definite culturing protocol in order to prevent bias | Chugh et al., 2021; Lamers et al., 2021; Mallapaty, 2021; Yu, 2021 | |
| Liver | - Investigated liver tissue damage of SARS-CoV-2 ex vivo. - Mimicking host-virus interaction due to retaining the biology of individual tissues such as preserving human-specific ACE2 + /TMPRSS2 + population of cholangiocytes | - Inability to reflect the cellular complexity of human hepatobiliary system for instance specific immune cell subsets -Lack of non-parenchymal cells -Presenting immature liver phenotype | Zhao et al., 2020; Lui et al., 2021; Youhanna et al., 2021; Yu, 2021 | |
SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; AKI, Acute kidney injury; MSC, Mesenchymal Stem Cell; IPSC, Induced pluripotent stem cells; BBB, Blood Brain Barrier; ACE2, Angiotensin-converting enzyme 2; TMPRSS2, Transmembrane protease; serine 2.