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. 2022 Nov 2;10:1005926. doi: 10.3389/fcell.2022.1005926

TABLE 8.

Summarizes the therapeutic approaches using iPSCs in COVID-19 associated diseases.

Sources Diseases Key findings Key molecules Signalling pathway involve Study group Year References
Alveolar organoids SARS-CoV-2 Lung organoids serve as a pathophysiological model for studying the mechanism of SARS-CoV-2 Remdesivir reduced the viral load of SARS-CoV-2 infection Down-regulated lipid metabolism upon SARS-CoV-2 infection Ciliated, club, and alveolar type 2 cells 2021 Pei et al. (2021)
Brain organoids Neurological complications Brain organoids as a platform to investigate the susceptibility to SARS-CoV-2 infection of brain cells, a mechanism of virus-induced brain dysfunction Choroid plexus organoids (CPOs) act as a better model system by expressing SARS-CoV-2 receptors at a high level and exhibit infection and pathogenesis at the cellular and molecular levels N/A Human IPSCs from healthy donors and convalescent serum from COVID-19 patients 2020 Jacob et al. (2020)
Retinal organoids Human eye problem Study whether ACE2 expression affects human retinal neurons during SARS-CoV-2 infection ACE2 plays an important role in the regulation of blood pressure and the expression of angiotensin II during inflammation. ACE 2 facilitates entry of SARS-CoV-2 infection N/A N/A 2021 Ahmad Mulyadi Lai et al. (2021)
Human IPSC-derived neural stem/progenitor cells (hiPSC-NS/PCs Central nervous system dysfunction The viral virulent factor CCN1 has been expressed in cells induced by SARS-CoV-2. CCN1 is involved in viral toxicity. HiPSC-NS/PCs were used as a model to study the SARS-CoV-2 infection-ACE2-CCN1 axis Compound 34 and γ-secretase inhibitor (GSI) help to reduce the CCN1 level N/A N/A 2020 Kase and Okano, (2020)
Human islets and adult hepatocyte and cholangiocyte organoids Studies on the viral tropism of SARS-CoV-2 and cellular responses to infection The expression profile and the permissiveness of pancreatic alpha and beta cells to infection by the pseudo-entry virus were confirmed in primary adult human islets. Hepatocytes and cholangiocytes from adult liver organoids were also tested for susceptibility to the SARS-CoV-2 virus The interaction of cytokine-cytokine receptors, IL-17 signaling, chemokine signaling pathway, TNF signalling pathway, and NF-κB signalling pathway has been overrepresented and upregulated Chemokine genes including CXCL1, CXCL3, CXCL5, CXCL6, and CCL20 were robustly upregulated, whereas key metabolic markers such as CYP7A1, CYP2A6 and CYP1A2 were significantly downregulated Cardiomyocytes, dopaminergic neurons, macrophages, microglia, and cortical neurons 2020 (L. Yang et al., 2020)
Cell metabolism was largely downregulated
human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) Cardiac injury Cardiomyocytes appeared to be less susceptible to infection and cytotoxicity caused by SARS-CoV-2 compared to TMPRSS2+ CaCo-2 cells. Cardiomyocyte infection is typically caused by exposure to a high local virus concentration and for a longer period Cathepsins L and B, which can also activate the virus, can also activate the S-protein Activation of interferon pathways is a typical transcriptional response to SARS-CoV-2 infection Caco-2 cells 2020 Bojkova et al. (2020)
A protease inhibitor, ALLM, which inhibits cathepsin L and B, reduced the expression of viral spike proteins
Organoids of human pluripotent stem cell-derived choroid plexus organoids SARS-CoV-2 Neurotropism Using an organoid platform, we provide information on the cellular susceptibility, pathogenesis, and treatment strategies associated with SARS-CoV-2 infection of brain cells. In addition, the choroid plexus is suggested to be a potentially important site for disease pathogenesis. CPOs express high levels of SARS-CoV-2 receptors, as the expression level is higher compared to other brain organoids Monolayer culture includes hiPSC-derived cortical neurons, astrocytes, and microglia, and brain organoids including hiPSC-derived cortical, hippocampal, hypothalamic, and midbrain organoids Nuclear factor B (NF-B) and mitogen-activated protein kinases (MAPK) are activated by stimulating tumor necrosis factor alpha (TNF-alpha), thus inducing both innate and adaptive immune responses. In other cells, this pathway has been shown to be activated after SARS-CoV-2 infection N/A 2020 Jacob et al. (2020)
Human-induced pluripotent stem-cell-derived kidney organoids Kidney fibrosis Kidney organoids can be successfully infected with SARS-CoV-2 with entry factors such as ACE2 and TMPRSS2. SARS-CoV-2 infected kidney cells induced increased profibrotic signaling, cellular damage, and higher inflammatory responses. This organoid study demonstrates the fundamental pathophysiological effects caused by kidney cell infection A protease inhibitor (MAT-POS-b3e365b9-1) was used to reduce intracellular viral RNA of SARS-CoV-2 The proinflammatory and fibrosis-driving pathway, such as tumor necrosis factor-alpha (TNFα), transforming growth factor beta (TGFβ), nuclear factor κB (NFκB), and JAK-STAT, shows higher activity in COVID-19 patients COVID-19 human kidney tissue 2022 Jansen et al. (2022)
Small intestinal epithelial cells derived from human-induced pluripotent stem cells (iPSCs) (iPSC-SIECs) Gastrointestinal complications Study whether iPSC-SIECs can be used as a model to investigate gastrointestinal problems. Remdesivir has the potential to reduce gastrointestinal symptoms N/A N/A Remdesivir and a coronavirus fusion inhibitor EK1 inhibit SARS-CoV-2 infection 2022 Yamada et al. (2022)