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Table 1 Representative use of PCLS as a translational model

From: Use of precision cut lung slices as a translational model for the study of lung biology

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]
  1. 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