Lung fibrosis model and methods of using the same
AssigneeDuke University
InventorsPurushothama Rao Tata, Aleksandra Tata, Arvind Konkimalla, Yoshihiko Kobayashi
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Abstract
The present disclosure provides a newly-identified transitional cell state in alveolar regeneration, models to ablate lung alveolar type-1 cells that leads to lung fibrosis and emphysema, a scalable, an ex vivo lung fibrosis model that uses co-cultured lung fibroblasts and pre-alveolar type-1 transitional cell state (PATS) for the use of disease modeling and drug screening, and methods of using same.
Claims37
A method of generating a lung injury organoid model, the method comprising:
- i) providing a co-culture of cells in a culture medium adapted for the culture of said cells, wherein the co-culture comprises pre-alveolar type-1 transitional cell state (PATS) cells and alveolar fibroblasts;
- ii) contacting the culture medium with one or more agents;
- and
- iii) analyzing the biological effect of the agent on at least one expression marker of the PATS cells and/or the alveolar fibroblasts relative to a control cell culture medium that has not been contacted by the agent.
A method of generating an ex vivo model for lung fibrosis, the method comprising:
- i) providing a culture of AEC1 cells that have undergone ablation in vivo in a culture medium adapted for the culture of said cells;
- ii) contacting the culture medium with one or more agents;
- and
- iii) analyzing the biological effect of the agent on at least one expression marker the AEC1 cells relative to a control cell culture medium that has not been contacted by the agent.
A method of identifying pre-alveolar type-1 transitional cell state (PATS) cells or PATS-like cells, the method comprising:
- i) obtaining alveolar cells;
- and
- ii) screening the cells for one or more markers,
- wherein the presence of the one or more markers indicates the presence of PATS cells or PATS-like cells.
A method of generating an in vivo tissue fibrosis model, the method comprising:
- i) introducing a genetic loss of PDGF ligands and/or PDGF receptor (PDGFR) signaling in a subject;
- and/or
- ii) administering an agent to a subject that can modulate PDGF-PDGFR signaling;
- and
- iii) analyzing cells from the subject to determine the biological effect of genetic loss of PDGF ligands and/or PDGF receptor (PDGFR) signaling and/or the biological effect of the agent that can modulate PDGF-PDGFR signaling relative to a control subject.
A method of generating an in vivo tissue fibrosis model, the method comprising:
- i) introducing a genetic loss of RUNX1, RUNX2, RUNX3, or CBFb in a subject;
- and/or
- ii) administering to the subject a RUNX1, RUNX2, RUNX3, or CBFb inhibitor;
- and
- iii) analyzing cells from the subject to determine the biological effect of the genetic loss of RUNX1, RUNX2, RUNX3, or CBFβ and/or the biological effect of the RUNX1, RUNX2, RUNX3, or CBFβ inhibitor relative to a control subject.
Dependencies are inferred from the claim text.