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US 2020/0270571 A1Published application
In vitro generation of thymic organoid from human pluripotent stem cells
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsRaul E. Vizcardo, Nicholas P. Restifo
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Abstract
Disclosed are methods of preparing thymic organoids according to embodiments of the invention. Also disclosed are methods of preparing thymic emigrant cells in vitro, according to embodiments of the invention. Also disclosed are methods of treating or preventing a condition in a mammal, e g , cancer.
Claims20
A method of preparing a thymic organoid in vitro, the method comprising:
- (i) differentiating pluripotent stem cells into endodermal cells in vitro;
- (ii) differentiating the endodermal cells into third pharyngeal pouch endodermal (PPE) cells in vitro;
- (iii) differentiating the third PPE cells into thymic epithelial progenitor-like cells (TEPLCs) in vitro;
- (iv) differentiating the TEPLCs into thymic epithelial progenitor cells (TEPCs) in an in vitro, three-dimensional culture;
- (v) differentiating the TEPCs into thymic epithelial cells (TECs) in the in vitro, three-dimensional culture in the presence of bone morphogenetic protein 4 (BMP4);
- and
- (vi) forming the TECs into a thymic organoid in the in vitro, three-dimensional culture,
- wherein the thymic organoid expresses any one or more of β5t, DLL4, and interleukin 7, and
- wherein the method does not comprise co-culturing the cells with mesenchyme or stromal cells.
6 more elements
The method of claim any 1, wherein the thymic organoid comprises keratin 5high/keratin 8low cells.
Dependencies are inferred from the claim text.