Table 1 |.
Comparison and contrast of methods to derive lung organoid model systems
| Bud tip progenitor organoid (routine passaging) | Patterned lung organoid (intact structure, no passage) | Human lung organoid | Lung bud organoid | Proximal airway organoids | Alveolar spheres | Alveolar organoids | Airway epithelial spheroids | ||
|---|---|---|---|---|---|---|---|---|---|
| ref. 17 | ref. 17 | refs. 15,16 | ref. 28 | ref. 27 | ref. 26 | refs. 29,35 | ref. 30 | ||
| In vitro | Time required for generation from hPSCs | ~3 weeks | ~6 weeks | ~8 weeks | ~10 weeks | ~3 weeks | ~4 weeks | ~4 weeks | ~4 weeks |
| Cell-sorting step required | No | No | No | No | Yes | Yes | Yes | Yes | |
| Mesenchyme present | No | No | Yes | Yes; minimal | No | No | No | No | |
| Airway epithelial structures | No | Yes | Yes | Yes | Yes | No | No | Yes | |
| Airway-like cells | No | Yes: SCGB1A1+ Club-like cells and MUC5AC/B+ goblet-like cells |
Yes: FOXJ1+ ACTTUB+ multiciliated-like cells, SCGB1A1+ Club-like cells, P63+ basal-like cells |
Yes: MUC5AC+MUC1+ goblet-like cells |
Yes: FOXJ1+ACTTUB+ multiciliated-like cells, SCGB3A2 Club-like cells, P63+KRT5+ basal-like cells, MUC5AC+ goblet-like cells |
No | No | Yes: FOXJ1+ACTTUB+ multiciliated cells, SCGB3A2 + Club-like cells, KRT5+ basal-like cells, MUC5AC+ goblet-like cells |
|
| Functional airwaycells | No | Yes: mucus secreted into organoid lumens | Not tested | Yes: mucus secreted into organoid lumens | Yes: mucus secreted into organoid lumens, beating multiciliated cells, and forskolin-induced swelling | No | No | Yes: mucus secreted into organoid lumen, beatingmulticiliated cells | |
| Alveolar-like cells | No | Yes: AECI and AECII-like cells (FGF7 alone in media) |
Yes: AECI and AECII-like cells |
Yes: AECII-like cells |
Yes: AECII-like cells |
Yes: AECII-like SFTPC+ cells |
Yes: AECI and AECII-like cells |
No | |
| Functional alveolarcells | No | Not tested | Not tested | Yes: cells uptake tagged SFTPB | Not tested | Yes: functional surfactant production | Not tested | No | |
| Epithelial budded/branch-like structures | No | Yes | No | Yes | No | No | No | No | |
| Functional (self-renewing, multilineage potential) bud tip progenitors | Yes | Yes | No | Not tested | Not tested | No | No | No | |
| Expandable organoids | Yes | No | No | No | No | Yes | Yes | No | |
| In vivo maturation | Time required for maturation in vivo | 6 weeks | Not tested | 8 weeks | 6–18 weeks | Not tested | Not tested | Not tested | Not tested |
| Transplantation into mouse fat pad/kidney capsule | Not tested | Not tested | Yes; maturation of adult airway structures and airway cell types including beating cilia and mucus secretion | Yes; maturation of airway structures and cell types including beating cilia and mucus secretion; maturation of alveolar type I and II cells | Not tested | Not tested | Not tested | Not tested | |
| Transplantation into injured mouse airway | Yes; successful engraftment and differentiation | Not tested | Not tested | Not tested | Not tested | Not tested | Not tested | Not tested | |
| Best suited for studies exploring: | • Epithelial lineage fate decisions • Fetal lung development • High-throughput drug/toxicology testing • Pathogen infection |
• Epithelial morphogenesis • Fetal lung development • Pathogen infection • Mucous cell metaplasia |
• Mesenchymal–epithelial interactions during development and disease (e.g., pulmonary fibrosis) • Pathogen infection |
• Epithelial morphogenesis • Pathogen infection • Mucous cell metaplasia |
• Adult diseases involving mucociliary function (CF, asthma) • Pathogen infection |
• Genetic alveolar disease • High-throughput drug/toxicology testing • Pathogen infection |
• Genetic alveolar disease • High-throughput drug/toxicology testing • Pathogen infection |
• Adult diseases involving mucociliary function (CF, asthma) • Pathogen infection |
|
| Not well suited for studies exploring: | • Adult epithelial disease modeling (e.g., CF, asthma) • Mesenchymal–epithelial interactions |
• Some adult disease modeling (e.g. CF, asthma) • Mesenchymal–epithelial interactions |
• Adult diseases involving mucociliary function (CF, asthma) • High-throughput drug/toxicology testing |
• Adult epithelial disease modeling (e.g. CF, asthma) • Mesenchymal–epithelial interactions |
• Mesenchymal–epithelial interactions • Alveolar diseases • Fetal lung development |
• Mesenchymal–epithelialinteractions • Airway diseases • Fetal lung development |
Mesenchymal–epithelial interactions; airway diseases | • Mesenchymal–epithelial interactions • Alveolar diseases • Fetal lung development |