Table 1.
Representative use of PCLS as a translational model
| Studies | PCLS origin | PCLS size | Culture conditions | Key findings | Reference |
|---|---|---|---|---|---|
| Wohlse et al. | Human donors | 250-μm thickness, 9-mm diameter | MEM with supplements; 37 °C, 5% CO2, and 100% air humidity |
•At least 3-day viability of PCLS •Immediate airway hyperresponsiveness of sensitized PCLS Inhibition of early allergic response of PCLS by blockade of leukotriene and thromboxane receptors |
[25] |
| Temann et al. | Human donors | 600-μm thickness, 8-mm diameter | DMEM/Ham’s F12; 37 °C, 5% CO2, 100% air humidity |
•At least 14-day viability of PCLS with normal metabolic activity, tissue homeostasis and structural integrity •Pro-inflammatory responses of PCLS to LPS stimulation •Re-call immune responses of PCLS against seasonal influenza vaccine and tetanus toxoid |
[26] |
| Bai et al. | Human donors | 250-μm thickness, diameter not shown | DMEM/Ham’s F12; 37 °C, 5% CO2, 100% air humidity | •A long-term storage of PCLS by cryopreservation without affecting overall cell viability, functions of immune cells, and contraction and relaxation of in response to specific agonists and antagonists | [27] |
| Cooper et al. | Human donors | 250-μm thickness, 8-mm diameter | Ham’s F12; 37 °C, 5% CO2, and 95% air humidity |
•Attenuation of isoproterenol-induced relaxation of PCLS by albuterol •Reduction of cell-surface β2-adrenergic receptors by albuterol •Inhibition of albuterol-induced desensitization of β2-adrenergic receptors in PCLS by dexamethasone pretreatment |
[28] |
| Alsafadi et al. | Human donors | 500-μm thickness, diameter not shown | DMEM/Ham’s F12; 37 °C, 5% CO2, humidified | •Induction of early fibrosis-like changes in PCLS by using a combination of profibrotic growth factors and signaling molecules | [29] |
| Banerjee et al. | Human donors | 250-μm thickness, 8-mm diameter | Ham’s F12; 37 °C, 5% CO2, and 95% air humidity |
•Inhibition of the carbachol-induced PCLS contraction by trichostatin A •Inhibition of the agonist-induced PCLS contraction by trichostatin A via decreasing the agonist-induced mobilization of calcium in airway smooth muscle |
[30] |
| Sturton et al. | Human donors, rat | 270 ± 10-μm thickness, 8-mm diameter | RPMI 1640 for human PCLS and DMEM for rat PCLS; 37 °C, 5% CO2, and 95% air humidity | •Similarity of potency, intrinsic efficacy, and onset of action of indacaterol, formoterol and salmeterol to reverse the carbachol (for human) or serotonin (for rat)-induced contraction in both human and rat PCLS | [31] |
| Kennedy et al. | Asthma donors | 250-μm thickness, diameter not shown | Ham’s F12; 37 °C, 5% CO2, and 95% air humidity |
•Increased il25, tslp, and il13 expression in asthma PCLS following RV39 infection •Increased carbachol-induced constriction in asthma PCLS after infection |
[32] |
| Ghosh et al. | Asthma donors | 350-μm thickness, 8-mm diameter | Ham’s F12; 37 °C, 5% CO2, and 95% air humidity |
•Stimulation of NO-sGC-cGMP pathway bronchodilated PCLS from healthy donors •Chronic NO exposure caused sGC to show hallmarks of oxidative damage that observed in asthmatic human lung |
[33] |
| Mercer et al. | IPF donors | 250-μm thickness, 8-mm diameter | DMEM with supplements; 37 °C, 10% CO2, and 100% air humidity |
•Active PI3K signalling within IPF fibrotic foci •PI3K/mTOR inhibitors reduced Akt phosphorylation in human IPF PCLS •PI3K/mTOR inhibitor reduced collagen formation markers in human IPF PCLS |
[34] |
| Van Dijk et al. | Mouse | 250-μm thickness, diameter not shown | DMEM with supplements; 37 °C, 5% CO2, and 95% air humidity |
•A significant increase in mean linear intercept of elastase-treated PCLS ex vivo •Disorganized elastin and collagen fibers of elastase-treated PCLS •Decreased alveolar Type I and II marker expression of elastase-treated PCLS •Enhanced methacholine-induced airway narrowing and impaired chloroquine-induced airway opening of elastase-treated PCLS |
[35] |
| Tatler et al. | Bleomycin-treated mouse | 150-μm thickness, diameter not shown | DMEM; 37 °C, 5% CO2 |
•Significantly higher levels of collagen in PCLS from bleomycin-treated mouse •Caffeine significantly reduced collagen deposition over 5 days within bleomycin-PCLS |
[36] |
| Henjakovic et al. | chemical allergen-sensitized mouse | 220-μm thickness, diameter not shown | MEM with supplements; 37 °C, 5% CO2, and 100% air humidity |
•High doses of TMA and DNCB induced cell dearh, tissue damage, and nuclear degeneration in naïve PCLS •TMA significantly decreased methacholine-induced bronchoconstriction |
[37] |
| Lin et al. | Rat | 300-μm thickness, diameter not shown | MEM; 37 °C incubator, 75% N2, 20% O2, 5% CO2, in scintillation vials on a bench roller | •CdCl2/TGF-β1-induced lung injury similar to that in early lung fibrogenesis in human | [38] |
MEM Minimum Essential Medium, DMEM Dulbecco’s Modified Eagle Medium, NO nitric oxide, sGC soluble guanylate cyclase, cGMP cyclic guanosine monophosphate, PI3K Phosphoinositide 3-kinase, mTOR mammalian target of rapamycin, TMA trimellitic anhydride, DNCB 2,4-dinitrochlorobenzene