Use of alveolar or airway organoids for the treatment of lung diseases and disorders
OwnerCarla F. KIM, Sharon M. LOUIE +2inventors
InventorsCarla F. KIM, Sharon M. LOUIE, Erhan ARARAT, David RAISER
Life of this patent
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Abstract
Various aspects described herein provide methods of generating alveolar or alveolar/airway organoids from a population of lung cells to differentiate into alveolar or alveolar/airway organoids. Also provided herein are methods and compositions for treating lung disease comprising transplantation of the alveolar or alveolar/airway organoids, or a cell isolated therefrom to a subject.
Claims43
A method for treating a lung disease or disorder, or a lung injury in a subject, the method comprising administering to a subject, intratracheally, a composition comprising an alveolar organoid, airway organoid, or an isolated cell thereof,
- wherein the alveolar organoid or airway organoid are provided or optionally produced in vitro or ex vivo from a lung cell by culturing the lung cell in a 3-dimensional culture for a time and under conditions sufficient to produce an alveolar organoid or airway organoid, and
- wherein the alveolar organoid, airway organoid or cell thereof functionally engrafts into the lung, thereby treating the lung disease or disorder or lung injury in the subject.
A method for treating a lung disease or disorder, or a lung injury, the method comprising administering to a subject, intratracheally, a composition comprising an alveolar organoid, airway organoid, or an isolated cell thereof,
- wherein the alveolar organoid or cell thereof is CD31/CD45−, Epcam+ and Sca1− in murine cells, or CD31−/CD45−, Epcam+, and HTII-280+ in human cells),
- wherein the airway organoid or cell thereof is CD31/CD45−, Epcam+ and Sca1+ in murine cells, or CD31−/CD45−, Epcam+, and NGFR+ in human cells, and
- wherein the alveolar organoid, airway organoid or cell thereof functionally engrafts into the lung, thereby treating the lung disease or disorder or lung injury in the subject.
A mouse useful for modelling COVID-19 induced lung injury, comprising a recipient mouse having engrafted human primary lung cells or iPS-derived lung cells,
- wherein the mouse is made by the process of administering, intratracheally, an airway organoid, or an isolated cell thereof into the recipient mouse,
- wherein the airway organoid or cell thereof is CD31/CD45−, Epcam+ and Sca1+, and
- wherein the airway organoid or cell thereof functionally engrafts into the lung,
A transplant composition comprising a human alveolar organoid, wherein the cells of the alveolar organoid are CD31/CD45−, Epcam+and Sca1− in murine cells, or CD31−/CD45−, Epcam+, and HTII-280+ in human cells.
A transplant composition comprising a human airway organoid, wherein the cells of the airway organoid are CD31/CD45−, Epcam+ and Sca1+ in murine cells, or CD31−/CD45−, Epcam+, and NGFR+ in human cells.
A method of treating a lung disease or disorder in a subject, the method comprising:
- (a) obtaining an iPSC and differentiating the iPSC to a lung cell;
- (b) culturing the lung cell of step (a) in a Basic 3D medium or CK-DCI for a sufficient amount of time to allow the lung cell to differentiate into alveolar organoids;
- and
- (c) transplanting the alveolar organoid or an isolated cell population thereof of step (b) via intratracheal delivery in a subject in need thereof,
- wherein transplanting results in engraftment of the alveolar organoid or isolated cell population thereof.
A method of treating a lung disease or disorder in a subject, the method comprising:
- (a) obtaining an iPSC and differentiating the iPSC to an alveolar cell;
- and
- (b) transplanting the alveolar cell or population thereof of step (a) via intratracheal delivery in a subject in need thereof,
- wherein transplanting results in engraftment of the alveolar cell.
A method of increasing the efficiency of engraftment of an alveolar cell following an alveolar cell transplant, the method comprising co-administering an immunosuppressant agent with the transplantation.
Dependencies are inferred from the claim text.