IP Library › Granted Patent US 12,241,090
Granted Patent B2
US 12,241,090 · App. 17/305,196 · Granted Mar 4, 2025

Methods and systems for converting precursor cells into gastric tissues through directed differentiation

Inventors: James Macormack Wells (Cincinnati, OH); Kyle William McCracken (Cincinnati, OH)
Assignee: Children's Hospital Medical Center
C12N5/0697C12N5/0679C12N2501/11C12N2501/113C12N2501/115C12N2501/119C12N2501/155C12N2501/16C12N2501/385C12N2501/415C12N2501/727C12N2506/02C12N2506/45
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Quick Facts
Patent No.
US 12,241,090
App. No.
17/305,196
Granted
Mar 4, 2025
Kind
B2
Abstract

Disclosed are methods of inducing formation of a gastric cells and/or a gastric tissue, such as in the form of a gastric organoid. The formation of gastric cells and/or tissue may be carried out by the activating and/or inhibiting of one or more signaling pathways within a precursor cell. Also disclosed are methods for using the disclosed gastric cells, gastric tissues, and/or gastric organoids derived from precursor cells.

Claims (19)

1. A human gastric organoid (hGO), characterized by:

a) a lumen and glandular epithelium;

b) MUC5AC+ surface mucous cells that secrete mucus into the lumen and TFF2+ mucous gland cells; and

c) chromogranin A (CHGA)-positive endocrine cells.

2. The hGO of claim 1 , wherein the hGO comprises antrum gastric tissue, further characterized by expression of the antrum-specific marker PDX1.

3. The hGO of claim 1 , wherein the hGO comprises fundus gastric tissue, further characterized by expression of fundus-specific markers IRX3 and IRX5, and repression of PDX1 relative to antrum gastric tissue.

4. The hGO of claim 1 , wherein the hGO is derived from definitive endoderm.

5. The hGO of claim 4 , wherein the definitive endoderm is derived from a pluripotent stem cell.

6. The hGO of claim 1 , wherein the hGO is further characterized by:

d) a mesenchyme comprising FOXF1/VIMENTIN-positive submucosal fibroblasts and VIMENTIN/ALPHA-SM-ACTIN (SMA)-expressing subepithelial fibroblasts; and

e) lacking differentiated layers of smooth muscle.

7. The hGO of claim 1 , wherein the hGO is about 1 mm to about 4 mm in diameter.

8. The hGO of claim 1 , wherein the hGO comprises gastric glands and pits.

9. The hGO of claim 1 , wherein the hGO comprises a progenitor cell niche, further characterized by basally located zones of proliferation and SOX9 expression.

10. The hGO of claim 1 , wherein the hGO is further characterized by gastrin, ghrelin, somatostatin, and serotonin (5-HT) expression.

11. The hGO of claim 1 , wherein the hGO comprises Helicobacter pylori in the lumen.

12. The hGO of claim 4 , wherein the definitive endoderm is derived from an induced pluripotent stem cell.

13. The hGO of claim 11 , wherein the hGO comprises c-Met phosphorylation.

14. The hGO of claim 11 , wherein the hGO comprises PDX1 + epithelial cell proliferation.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 8, 2024
From: MCCRACKEN, KYLE WILLIAM; WELLS, JAMES MACORMACK
To: CHILDREN'S HOSPITAL MEDICAL CENTER
Reel/Frame 067033/0640 →
Continuity (4)
Continuation 16188597 · Nov 13, 2018
Continuation 15312939
Provisional Application 62003719 · May 28, 2014
Related Publication 20220056420A1 · Feb 24, 2022
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