IP Library › Granted Patent US 12,613,236
Granted Patent B2
US 12,613,236 · App. 17/763,991 · Granted Apr 28, 2026

Lung fibrosis model and methods of using the same

Inventors: Purushothama Rao Tata (Durham, NC); Aleksandra Tata (Durham, NC); Arvind Konkimalla (Durham, NC); Yoshihiko Kobayashi (Durham, NC)
Assignee: DUKE UNIVERSITY
G01N33/5023C12N5/0688G01N33/5088C12N2501/135C12N2502/27
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Quick Facts
Patent No.
US 12,613,236
App. No.
17/763,991
Granted
Apr 28, 2026
Kind
B2
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.

Claims (19)

1 . A method for drug screening on a lung injury organoid model, the method comprising:

providing in a culture medium a co-culture of cells comprising pre-alveolar type-1 transitional cell state (PATS) cells and alveolar fibroblasts; and

screening a drug for a biological effect by

contacting the culture medium with a drug; and

measuring accumulation of PATS cells and/or expression of at least one marker of PATS cells.

2 . The method of claim 1 , wherein the PATS cells are isolated from diseased tissue.

3 . The method of claim 2 , wherein the diseased tissue is chronic obstructive pulmonary disease (COPD) lung tissue, pulmonary fibrosis lung tissue, idiopathic pulmonary fibrosis lung tissue, emphysema lung tissue, lung cancer tissue, Sarcoidosis lung tissue, interstitial pneumonia lung tissue, sepsis lung tissue, lung tissue having viral and bacterial infections, acute respiratory distress syndrome lung tissue, and bronchopulmonary dysplasia lung tissue.

4 . The method of claim 1 , wherein the PATS cells are generated by exposing lung epithelial cells to an injury-causing agent in vivo or in vitro.

5 . The method of claim 4 , wherein the injury-causing agent is bleomycin, diphtheria toxin (DT), tamoxifen, irradiation, a virus, a bacterium, or a fungus.

6 . The method of claim 1 , wherein the alveolar fibroblasts are lipofibroblasts.

7 . The method of claim 1 , wherein the culture medium comprises a platelet-derived growth factor receptor (PDGFR) ligand or an agent that is capable of maintaining platelet-derived growth factor receptor A (PDGFRA) expression.

8 . The method of claim 7 , wherein the PDGFR ligand is platelet-derived growth factor subunit A (PDGFA), platelet-derived growth factor subunit B (PDGFB), platelet-derived growth factor subunit C (PDGFC), and/or platelet-derived growth factor subunit D (PDGFD).

9 . The method of claim 2 , wherein the agent is Ro 5-3335, AI-10-49 or other molecules that regulate runt-related transcription factor (RUNX) or core binding factor (CBF) proteins.

10 . The method of claim 1 , wherein the at least one marker of PATS cells comprises CLDN4, KRT19, SFN, LGALS3, SOX4, S100A2, PTGS2, KRT17, KRT8, CALS1, MMP7, PRSS2, IGFBP7, COL1A1, MDK, TAGLN, GDF15, TM4SF1 TP63, and/or CTSE.

11 . The method of claim 10 , wherein the one or more markers is CLDN4, LGALS3, and LGALS3.

12 . The method of claim 10 , wherein the one or more markers is CLDN4, KRT19, and SFN, or wherein the one or more markers is CALD1, PRSS2, MMP7, and S100A2.

13 . The method of claim 1 , wherein the accumulation of PATS cells and/or the expression of at least one marker of PATS cells are measured relative to a control cell culture medium, wherein the control cell culture medium has not been contacted by the drug.

14 . The method of claim 13 , wherein an increase of the accumulation of PATS cells and/or an increase in the expression of at least one marker of PATS cells relative to a control cell culture medium indicates the presence or persistence of fibrosis.

15 . The method of claim 13 , wherein a decrease of the accumulation of PATS cells and/or a decrease in the expression of at least one marker of PATS cells indicates that the drug can treat fibrosis.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 30, 2023
From: TATA, PURUSHOTHAMA RAO; TATA, ALEKSANDRA; KONKIMALLA, ARVIND; KOBAYASHI, YOSHIHIKO
To: DUKE UNIVERSITY
Reel/Frame 065722/0582 →
Continuity (3)
Provisional Application 62975294 · Feb 12, 2020
Provisional Application 62906241 · Sep 26, 2019
Related Publication 20220341915A1 · Oct 27, 2022
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