Fibrosis model and methods of use thereof
AssigneeThe Regents of the University of Colorado, a body corporate
InventorsDavid Schwartz, Ian Stancil
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Abstract
A method of screening a test compound, e.g., a fibrosis or IPF inhibitor, for induction of an unjammed-to-jammed transition (UJT) in fibrotic primary human bronchial epithelial cells (HBECs) isolated from a subject with a fibrotic lung disease includes culturing the fibrotic primary HBECs at an air-liquid interface for a time sufficient to provide a differentiated pseudostratified epithelium contacting the cultured cells with the test compound; and monitoring the motility of the cultured cells to identify the cultured cells as moving or stationary; wherein stationary cultured cells indicate that the test compound induces the UJT. Also included are methods of identifying lung fibrosis biomarkers.
Claims20
A method of screening a test compound for induction of an unjammed-to-jammed transition (UJT) in fibrotic primary human bronchial epithelial cells (HBECs) isolated from a subject with a fibrotic lung disease, comprising
- culturing the fibrotic primary HBECs at an air-liquid interface for a time sufficient to provide a differentiated pseudostratified epithelium;
- contacting the cultured cells with the test compound;
- and
- monitoring the motility of the cultured cells to identify the cultured cells as moving or stationary;
- wherein stationary cultured cells indicate that the test compound induces the UJT.
A method of identifying a lung fibrosis biomarker associated with induction of an unjammed-to-jammed transition (UJT) in fibrotic primary human bronchial epithelial cells (HBECs) isolated from a subject with a fibrotic lung disease, comprising
- culturing the fibrotic primary HBECs at an air-liquid interface for a time sufficient to provide a differentiated pseudostratified epithelium;
- contacting the cultured cells with the biomarker or an expression vector for the biomarker;
- and
- monitoring the motility of the cultured cells to identify the cultured cells as moving or stationary;
- wherein stationary cultured cells indicate that the biomarker induces the UJT.
A method for inducing a jammed phase in airway epithelial cells comprising administering one or more composition comprising one or more EGFR inhibitor, IL-6 inhibitor, IL-6 pathway inhibitor, ERBB inhibitor, YAP inhibitor, SRC inhibitor, PI3K inhibitor, PDK1 inhibitor or a combination thereof, in an amount sufficient to induce said jammed phase.
Dependencies are inferred from the claim text.