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. 2023 Jul 26;32(169):230042. doi: 10.1183/16000617.0042-2023

TABLE 1.

Overview of the use of the different 3D in vitro systems to model healthy and diseased human lungs

PCLS Organoids# Lung ECM-derived hydrogels Lung-on-chip
Healthy Both alveolar and airway:
Bronchoconstriction assay [18, 85]
Response to drugs or industrial  chemicals [86]
Long-term (14 days) [87, 88]
Indacaterol efficacy [89]		 Airway:
From adult stem cells [90, 91]
From PSCs [49, 92]
With bronchial epithelial cells, lung  fibroblasts and endothelial cells [93]
Alveolar:
From PSCs [94–96]
Both alveolar and airway:
Human fetal lung-derived  organoids [97]
 Both alveolar and airway:
Human lung ECM hydrogels and  comparison to native tissue [54]		 Airway:
With epithelial cells only [98]
Epithelial–vascular interface [99]
With fibroblast compartment [100]
Epithelial–ECM–smooth muscle  interface [101]
Epithelial–ECM–vascular  interface [102]
Cell extravasation [103]
Alveolar:
Alveolar–capillary interface [70]
Alveolar acini with immune  compartment [104]
With micro-diaphragm [76]
With inverse opal gelatine  hydrogel [105]
With biological and stretchable  membrane [79]
With fibroblast compartment [75]
Asthma Airway only:
Effect of soluble guanylate cyclase on  bronchodilation [106]
Asthma mediators [107]
β2-agonist efficacy modulated by  steroids [108]
Rhinovirus infection: increased IL-13,  IL-25 and thymic stromal  lymphopoietin [109]		 Airway only:
Notch2 role in goblet cell  metaplasia [110]		 Airway only:
IL-13-induced asthma [99]
IL-13 and viral-induced  exacerbations [111]
COPD Alveolar only:
CS model±viral exacerbations
FZD4 inhibitor efficiency in  COPD patient  PCLS [112]
Wnt/β-catenin signal activation  efficiency [22]		 Alveolar only:
COPD patient-derived epithelial cell  organoids [113]
Emphysematous alveolar epithelial  cells [42]		 Both alveolar and airway:
COPD lung ECM hydrogels and  comparison to native tissue [54]		 Airway:
With COPD epithelial cells, poly-I:C  induced [99]
Cigarette smoke induced [73, 114]
Alveolar:
Cigarette smoke induced [105]
With emphysematous cells [42]
Cystic fibrosis Airway:
From patient-derived adult stem  cells [46]
From patient-derived PSCs [50, 115]
From multipotent human foregut stem  cells with cystic fibrosis  transmembrane conductance  regulator mutation [116]
Not categorised:
Nasospheres for drug testing [117, 118]		 Both alveolar and airway:
With epithelial cells from CF  patients [100]
Lung fibrosis Alveolar only:
IPF model with cytokines [24]
From IPF patients [25]		 Alveolar only:
Hermansky–Pudlak syndrome [48]
Hermansky–Pudlak syndrome mutation  in embryonic stem cell-derived  organoids [119]		 Both alveolar and airway:
IPF lung ECM hydrogels and  comparison to native tissue [54]		 Both alveolar and airway:
With IPF fibroblasts [100]
Alveolar:
With epithelial cells (wound-healing  and stretch) [120]
Cancer Not categorised:
Kras mutation model [121]
Non-small-cell lung cancer [122]
T-cell infiltration [123]		 Not categorised:
From patient-derived adult stem  cells [46]
Patient-derived organoids:
Non-small-cell [124]
Adenocarcinoma [125]
Five different subtypes [126]
Co-cultured with endogenous  tumour-infiltrating lymphocytes [127]		 Not categorised:
Non-small-cell lung cancer [128, 129]
Mesothelioma [128]
Safety studies [130]

Only the studies using human-origin cells and ECM were included in the table. PCLS: precision-cut lung slice; ECM: extracellular matrix; PSC: pluripotent stem cell; iPSC: induced pluripotent stem cell; IL: interleukin; COPD: chronic obstructive pulmonary disease; CS: cigarette smoke; poly-I:C: polyinosinic:polycytidylic acid; IPF: idiopathic pulmonary fibrosis. #: studies using the following terminology were included under the “organoids” section: spheroids, tracheosphere, bronchosphere, alveolosphere, nasosphere and organoids; : studies aiming at building lung tissues for transplantation were not included in this table.