A drug screen with approved compounds identifies amlexanox as a novel Wnt/β‐catenin activator inducing lung epithelial organoid formation

Costa, Rita; Wagner, Darcy E.; Doryab, Ali; Santis, Martina M. De; Schorpp, Kenji; Rothenaigner, Ina; Lehmann, Mareike; Baarsma, Hoeke A.; Liu, Xueping; Schmid, Otmar; Campillos, Mónica; Yildirim, Ali Önder; Hadian, Kamyar; Königshoff, Mélanie

doi:10.1111/bph.15581

Cited by 13 publications

(8 citation statements)

References 69 publications

(113 reference statements)

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“…Distal organoid formation was done with murine lung fibroblasts (CCL206; American Type Culture Collection [ATCC]) as stromal support cells, as previously described ( Costa et al., 2021 ). Briefly, proliferation of CCL206 cells was inhibited by treatment with 10 μg/mL mitomycin C (M4287; Sigma-Aldrich) for 1 h at 37°C followed by 2 h incubation in CCL206 culture medium.…”

Section: Methodsmentioning

confidence: 99%

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

Alsafadi¹,

Stegmayr²,

Ptasinski³

et al. 2022

Stem Cell Reports

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Section: Methodsmentioning

confidence: 99%

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

Alsafadi¹,

Stegmayr²,

Ptasinski³

et al. 2022

Stem Cell Reports

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“…Distal progenitor cells for both the classic and 3DLD device were isolated as previously described (Jansing et al ., 2018). Distal organoid formation was performed with CCL206 cells (ATCC), murine lung fibroblasts (Mlg), as stromal support cells previously described (Costa et al, 2021). Further details for cell isolation and organoid formation, collection, fixation and imaging can be found in supplemental experimental procedures.…”

Section: Methodsmentioning

confidence: 99%

“…Several different in vitro and in vivo approaches have been used to identify the cell types involved in lung repair and regeneration. In vitro studies of isolated cells on tissue culture plastic or floating collagen gels were initially critical in characterizing the transition of ATII to ATI cells (Danto et al, 1995). In addition, in vivo lineage tracing has been instrumental in identifying several of the regionally specific progenitor populations (Tata and Rajagopal, 2017).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

Alsafadi

Stegmayr

Ptasinski

et al. 2022

Preprint

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SummaryThe respiratory epithelium consists of multiple, functionally distinct cell-types and is maintained by regionally-specific progenitor populations which repair the epithelium following injury. Several in vitro methods exist for studying lung epithelial repair using primary murine lung epithelial cells, but isolation methods are hampered by a lack of surface markers distinguishing epithelial progenitors along the respiratory epithelium. Here, we developed a 3D-printed lobe divider (3DLD) to aid in simultaneous isolation of proximal versus distal lung epithelial progenitors from individual mice which give rise to differentiated epithelia in multiple in vitro assays. In contrast to 3DLD-isolated distal progenitor cells, classic manual tracheal ligation methods followed by lobe removal resulted in co-isolation of rare proximal progenitors with distal cells which altered the transcriptional landscape of distal organoid cultures. Thus, cell isolation with the 3DLD generates reproducible distal versus proximal progenitor populations and minimizes the potential for contaminating populations to confound in vitro assays.Highlights3DLD reproducibly separates lung lobes and extrapulmonary airways (bronchi/trachea)3DLD cell isolation yields consistent isolation of distal epithelial cells (DECs)Contamination of proximal cells in classic DEC isolations may alter in vitro results3DLD allows for simultaneous isolation of proximal and DECs from single animalseTOC blurbAlsafadi et al. describes a new method for simultaneous isolation of lung epithelial proximal and distal progenitors using the aid of a 3D printed device (3DLD). Both isolated cell types differentiate in multiple in vitro assays. The 3DLD guide minimized contamination of proximal cells in distal cell isolations whose presence can alter the transcriptional landscape of distal epithelial organoids.

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“…Further studies revealed that expression of clock-pathway genes was distorted by cigarette smoke and prostaglandin I2 as well as prostacyclin were able to correct this effect and might therefore contribute to lung regeneration. Another drug-screening approach was used by C osta et al [ 100 ] with Food and Drug Administration-approved drugs using a Wnt-pathway reporter cell line, a key pathway in lung regeneration and repair. A luciferase assay in a Wnt-reporter cell line identified amlexanox as a possible Wnt-pathway activator.…”

Section: Year In Review: Preclinical Discovery and Testing Of New App...mentioning

confidence: 99%

ERS International Congress 2022: highlights from the Basic and Translational Science Assembly

et al. 2023

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In this review the Basic and Translational Science Assembly of the European Respiratory Society (ERS) provides an overview of the 2022 international conference highlights. We discuss the consequences of respiratory events from birth until old age regarding climate change-related alterations in air quality due to pollution caused by increased ozone, pollen, wildfires and fuel combustion as well as the increasing presence of microplastic and microfibres. Early life events such as the effect of hyperoxia in the context of bronchopulmonary dysplasia and crucial effects of the intrauterine environment in the context of preeclampsia were discussed. The Human Lung Cell Atlas (HLCA) was put forward as a new point of reference for healthy human lungs. The combination of single-cell RNA-sequencing and spatial data in the HLCA has enabled the discovery of new cell types/states, new niches and served as a platform that facilitates further investigation of mechanistic perturbations. The role of cell death modalities in regulating the onset and progression of chronic lung diseases and its potential as a therapeutic target was also discussed. Translational studies identified novel therapeutic targets and immunoregulatory mechanisms in asthma. Lastly, it was highlighted that the choice of regenerative therapeutic depends on disease severity, ranging from transplantation to cell therapies and regenerative pharmacology.

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A drug screen with approved compounds identifies amlexanox as a novel Wnt/β‐catenin activator inducing lung epithelial organoid formation

Abstract: Title: A drug screen with approved compounds identifies amlexanox as a novel Wnt/β-catenin activator inducing lung epithelial organoid formation

Cited by 13 publications

References 69 publications

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations

ERS International Congress 2022: highlights from the Basic and Translational Science Assembly

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