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Three-dimensional in vitro alveolar lung model, process for preparing said model, and its use for determining and/or predicting the sensitizing effects of inhalable products

A technology for inhalation and alveoli, applied in animal cells, biological testing, measuring devices, etc., can solve problems such as changing biological effect readings

Pending Publication Date: 2019-08-23
卢森堡理工学院
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  • Claims
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Problems solved by technology

Furthermore, exposure at the ALI allows realistic exposure to exogenous compounds without pre-dilution in cell culture media containing many biomolecules that will interact with the chemical under study, thereby potentially altering the readout of biological effects, Biological effects leading to unpredictable underestimation or overestimation

Method used

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  • Three-dimensional in vitro alveolar lung model, process for preparing said model, and its use for determining and/or predicting the sensitizing effects of inhalable products
  • Three-dimensional in vitro alveolar lung model, process for preparing said model, and its use for determining and/or predicting the sensitizing effects of inhalable products
  • Three-dimensional in vitro alveolar lung model, process for preparing said model, and its use for determining and/or predicting the sensitizing effects of inhalable products

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Embodiment Construction

[0022] More specifically, the macrophage-like cells are THP-1 cells differentiated with PMA (phorbol-12-myristate-13-acetate) or 1,25-dihydroxyvitamin D3, preferably with PMA differentiation. This differentiation is best accomplished within a few days: advantageously 3 to 10 days, preferably 5 days.

[0023] In the models of the present invention, all cells are immortalized mammalian cell lines, which are more stable cells than primary cells, and preferably immortalized human cell lines.

[0024] "Preferably", the alveolar type II epithelial cells are A549 cells.

[0025] And "preferably", the endothelial cells are EA.hy926 cells.

[0026] Also "preferably", said dendritic cells are undifferentiated THP-1 cells, which model the pores of human dendritic cells.

[0027] Dendritic cells are critical in the sensitization process, as these cells are responsible for recognizing and capturing antigens, thereby triggering an immune response.

[0028] Advantageously, the three-dime...

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Abstract

The invention relates to a three-dimensional in vitro alveolar lung model comprising essentially the four cells types as follows: alveolar type II epithelial cells able to secrete (lung laying) surfactant, endothelial cells which forms the inner lining of capillaries providing a permeable barrier, dendritic-like cells, such as non-differentiated THP-1, linking innate and adaptive immunity and macrophage-like cells, able to participate to defense mechanisms by ingesting foreign materials by phagocytosis. The invention also relates to a process for preparing said model, and its use for assessingthe irritation potential or toxicity of inhalable products such as particles or molecules on the alveolar barrier of lungs, and also for determining and / or predicting the sensitizing effects of inhalable products such as particles or molecules on the alveolar barrier of lungs.

Description

technical field [0001] The invention relates to a three-dimensional in vitro alveolar lung model and a preparation method of the model. [0002] The invention also relates to its use for assessing the irritative potential or toxicity of inhalable substances (such as respirable particles or molecules) to the alveolar barrier of the lung, and for determining and / or predicting the effect of inhalable substances (such as respirable particles or molecules) on Uses and methods for sensitizing effects of the alveolar barrier of the lung. Background technique [0003] Respiratory sensitization due to exposure to chemical products has increased over the past few decades, leading to increased morbidity. The wider use of synthetic compounds such as fragrances and industrial solvents has led to an exponential increase in the number of substances we may be exposed to every day. Some of these substances are known to cause respiratory sensitization, meaning they can trigger the developme...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N5/071C12N5/0784G01N33/50
CPCC12N5/0639C12N5/0688C12N5/0697C12N2502/1114C12N2502/1121C12N2502/1157C12N2502/27C12N2502/28C12N2503/04G01N33/5088G01N33/50A61K39/4615A61K39/4611A61K2121/00A61K2300/00
Inventor 阿林·沙里阿尔诺·古特莱贝托马索·塞尔基布伦海尔德·布洛梅克
Owner 卢森堡理工学院
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