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Table 2 Stem cell models for SARS-CoV-2

From: When stem cells meet COVID-19: recent advances, challenges and future perspectives

Stem cell model Cell types Culture method Immune response Key findings References
ASCs Liver bile duct-derived progenitor cells 3D Not discussed The liver damage in COVID-19 patients might result from direct cholangiocyte injury and consequent bile acid accumulation induced by viral infection Zhao et al. [98]
ASCs Alveolar type 2 cells 3D Type I response in both studies with an MOI of 1 and ISG stimulation WNT activity is crucial for hAT2 maintenance; AT2s express a SARS-CoV-2 receptor, ACE2, and are sensitive to virus infection; Low-dose IFN pre-treatment blocks SARS-CoV-2 replication in alveolospheres Youk et al. [26], Katsura et al. [99] and Tindle et al. [100]
ASCs Intestinal stem cells 2D IFNL2 and IFNL3 were highly induced and type I-III IFN response at 24 h after inoculation with an MOI of 3 Established the first expandable organoid culture system of bat
intestinal epithelium
Zhou et al. [101]
ASCs Primary gut endothelial stem cells Pseudo-stratified layer Increase in interferon genes 72 h post infection with an MOI of 0.1 Intestinal epithelium supports SARS-CoV-2 replication; SARS-CoV-2 induces a stronger interferon response than SARS-CoV in HIOs Lamers et al. [103]
ASCs Hepatocytes 3D Chemokine, IL-17, TNF and NFκB signaling at MOI 0.1 at 24 h Human hepatocyte organoids are permissive to SARS-CoV-2 infection Yang et al. [112]
ASCs Cholangiocytes 3D Chemokine and IL-17 signaling pathway activated at MOI 0.1 at 24 h Human cholangiocyte organoids are permissive to SARS-CoV-2 infection Yang et al. [112]
hPSC derived colonoids 3D TNF and IL-17 signatures reported after 24 h with an MOI of 0.1 Identified FDA-approved drug candidates, including imatinib and mycophenolic acid, as inhibitors of SARS-CoV-2 entry Han et al. [104]
hPSC derived alveolar type II-like cells; enterocytes   TNF, IL-17 signaling, and cytokine-cytokine
Receptor interaction at MOI 0.01 at 24 h
Identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid (MPA), and quinacrine dihydrochloride (QNHC) Chen et al. [105]
hPSC derived Airway cells 3D IL-6 and IL-18 significantly up-regulated at MOI 0.01 at 24 h Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2 Duan et al. [106]
iPSC derived Alveolar type 2 cells 3D Delayed type I interferon response with an MOI of 5 and ISG stimulation SARS-CoV-2 infection of pluripotent Stem Cell-Derived Human Lung AT2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response Huang et al. [107]
hPSC derived Cardiomyocytes 2D Type I interferon response and ISG stimulation at MOI 0.01 Androgen Signaling Regulates SARS-CoV-2 10
Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men
Samuel et al. [108]
iPSC derived Neurons 2D/3D Not discussed Neurospheres were permissive to SARS-CoV-2 infection and supported productive virus replication Zhang et al. [110]
Ramani et al. [111]
hPSC derived Microglia 2D Not discussed hPSC-derived microglia cells are permissive to SARS-CoV-2 infection. hPSC-derived cells or organoids show similar chemokine responses as COVID-19 tissues Yang et al. [112]
hPSC derived Endocrine 3D Chemokine induction at 24 h after MOI 0.01 hPSC-derived pancreatic endocrine cells are permissive to SARS-CoV-2 infection Yang et al. [112]
hPSC derived Cardiomyocytes 3D IL-11, IL-1B significantly up-regulated at MOI 0.1 at 72 h hPSC-derived cardiomyocytes are permissive to SARS-CoV-2 infection Perez-Bermejo et al. [113], Bojkova et al. [114], Sharma et al. [115] and Yanagida et al. [116]
iPSC derived Capillary; kidney 3D Not discussed SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids. hrsACE2 can significantly block early stages of SARS-CoV-2 infections Monteil et al. [117]
  1. ASCs, adult stem cells; iPSC, induced pluripotent stem cell; MOI, multiplicity of infection; hAT2, human lung alveolar type 2; ISG:IFN-stimulated gene; ACE2, angiotensin converting enzyme 2; hrsACE2, human recombinant soluble ACE2; hSIOs, human small intestinal organoids