Lung organoid culture

Zimmermann, Bernd

doi:10.1111/j.1432-0436.1987.tb00183.x

Cited by 57 publications

(31 citation statements)

References 156 publications

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“…Prior studies have demonstrated that dissociated mouse E14.5 lung cells cultured as high-density mixed cell aggregates (lung organoids) at an air-fluid interface can form lung histotypic structures, including alveolar-like spheres, lined by appropriately differentiated epithelial cells (17). We have improved upon this method to achieve extensive development of lung organoids in vivo that recapitulated normal development.…”

Section: Introductionmentioning

confidence: 99%

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Chapman

Li²,

Alexander³

et al. 2011

J. Clin. Invest.

387

257

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Laminins and their integrin receptors are implicated in epithelial cell differentiation and progenitor cell maintenance. We report here that a previously unrecognized subpopulation of mouse alveolar epithelial cells (AECs) expressing the laminin receptor α6β4, but little or no pro-surfactant C (pro-SPC), is endowed with regenerative potential. Ex vivo, this subpopulation expanded clonally as progenitors but also differentiated toward mature cell types. Integrin β4 itself was not required for AEC proliferation or differentiation. An in vivo embryonic lung organoid assay, which we believe to be novel, was used to show that purified β4 + adult AECs admixed with E14.5 lung single-cell suspensions and implanted under kidney capsules self-organized into distinct Clara cell 10-kDa secretory protein (CC10 + ) airway-like and SPC + saccular structures within 6 days. Using a bleomycin model of lung injury and an SPC-driven inducible cre to fate-map AECs, we found the majority of type II AECs in fibrotic areas were not derived from preexisting type II AECs, demonstrating that SPC -progenitor cells replenished type II AECs during repair. Our findings support the idea that there is a stable AEC progenitor population in the adult lung, provide in vivo evidence of AEC progenitor cell differentiation after parenchymal injury, and identify a strong candidate progenitor cell for maintenance of type II AECs during lung repair.

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Section: Introductionmentioning

confidence: 99%

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Chapman

Li²,

Alexander³

et al. 2011

J. Clin. Invest.

387

257

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“…The lungs of the fetuses were pooled and organoid cultures were prepared according to Zimmermann [23].…”

Section: Methodsmentioning

confidence: 99%

“…For the determination of the morphological lung maturation we performed transmission electron microscopy [23]. The sec-Brought to you by | University of Glasgow Library Authenticated Download Date | 6/25/15 5:55 AM tions were viewed under a Siemens EM 101 electron microscope at 80 kV.…”

Section: Electron Microscopy and Determination Of Morphogenetic Develmentioning

confidence: 99%

“…The sec-Brought to you by | University of Glasgow Library Authenticated Download Date | 6/25/15 5:55 AM tions were viewed under a Siemens EM 101 electron microscope at 80 kV. The best way to determine the morphological lung maturation is the pure description of the subjective findings and the illustration by characteristic electron microscopical images [20,22,23]. Therefore a semiquantitative score was established describing changes in the morphogenesis of lung histotypic structures, differentiation of pneumocytes type II, lamellar body (LB) synthesis and secretion: Thereby either minus 1Ϫ2 points for degrees of a poor lung development or plus 1Ϫ2 points are used for an improved lung development compared to the control standard of zero.…”

Section: Electron Microscopy and Determination Of Morphogenetic Develmentioning

confidence: 99%

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Effect of dexamethasone, triiodothyronine and dimethyl-isopropyl-thyronine on lung maturation of the fetal rat lung

Hundertmark¹,

Ragosch²,

Zimmermann³

et al. 1999

Journal of Perinatal Medicine

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Our purpose was to elucidate why clinical studies have up to now failed to demonstrate a positive effect of TRH combined with glucocorticosteroids on fetal lung maturity. Morphological and biochemical lung maturation were determined by electron microscopy, choline incorporation, and surfactant-protein-A m-RNA synthesis in rat lung organoid cultures after exposure with a series of concentrations of dexamethasone, triiodothyronine, and dimethyl-isopropyl-thyronine. Thyroid hormones improved morphogenesis of lung histotypic structures but had a negative effect on surfactant synthesis whereas glucocorticosteroids had a positive effect on the surfactant synthesis but a negative effect on morphogenesis. The combination of both substances even had the most negative effect on morphogenesis. Since morphogenesis of lung histotypic structures is prerequisite for surfactant synthesis and secretion, we hypothesize that a sequential treatment of thyroid hormones to improve morphogenesis followed by the application of glucocorticosteroids might be an option to improve neonatal lung function.

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“…Using the orga noid culture (micro mass culture) 'high density' of Trowell [20], we investigated cartilage breakdown in a coculture system consisting of mouse peritoneal macrophages and chondroblasts/chondrocytes derived from blastemal or precartilage cells of limb buds from day-12 mouse em bryos. Due to the high cell density and the close intercellu lar contacts, this culture model offers optimal conditions for differentiation [21][22][23] of both cell types and subse quent synthesis of the cartilage-specific matrix [24], This paper describes the effects of mouse peritoneal macrophages on cartilage matrix and integrins of chon drocytes in vitro by morphological and immunomorphological methods.…”

Section: Introductionmentioning

confidence: 99%

Influence of Mouse Peritoneal Macrophages on Cartilage Matrix and Integrins in vitro

Shakibaei

Mohamed-Ali

1994

Pathobiology

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The problem of cartilage breakdown in rheumatoid arthritis can partially be studied using in vitro techniques. Among the numerous models, organoid (high density) cultures have proved to be quite suited for these purposes. Chondroblasts/chondrocytes, obtained by cultivating precartilage cells of limb buds from day-12 mouse embryos, were cocultivated with mouse peritoneal macrophages in high-density or monolayer cultures. The result was an extensive breakdown of the cartilage matrix. Numerous chondrocytes detached from the matrix and became fibroblast-like cells. Immunomorphological methods showed that collagen type II, fibronectin and several integrins (β1-, α3-, and α5β1 types) disappeared from the surface of chondrocytes. These pathological findings in cartilage tissue could be due to degradative products of macrophages and also chondrocytes. The in vitro model introduced here should be useful for studying matrix components and the turnover of matrix receptors of cartilage tissue in vivo under pathological conditions.

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Lung organoid culture

Cited by 57 publications

References 156 publications

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Integrin α6β4 identifies an adult distal lung epithelial population with regenerative potential in mice

Effect of dexamethasone, triiodothyronine and dimethyl-isopropyl-thyronine on lung maturation of the fetal rat lung

Influence of Mouse Peritoneal Macrophages on Cartilage Matrix and Integrins in vitro

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