Table 2.
Stem cell models for SARS-CoV-2
| 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] |
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