CORNEAL EPITHELIOID CELLS DERIVED FROM SURFACE ECTODERMAL CELLS

• US 20180148685A1
• Filed: 01/12/2016
• Published: 05/31/2018
• Est. Priority Date: 01/13/2015
• Status: Active Grant

• Current Assignee: Osaka University
• Original Assignee: Osaka University
• Inventors: Nishida, Kohji, SASAMOTO, Yuzuru, HAYASHI, Ryuhei
• Granted Patent: US 10,457,913 B2
• Time in Patent Office: Days
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/60 Transcription factors
• CPC Class Codes: C12N 2501/603 Oct-3/4
• CPC Class Codes: C12N 2501/604 Klf-4
• CPC Class Codes: C12N 2506/097 from oral mucosa cells
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2740/15043 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 5/0602 Vertebrate cells
• CPC Class Codes: C12N 5/0621 Eye cells, e.g. cornea, iris pigmented cells photoreceptors C12N5/062
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material

Abstract

The present invention relates to a method for inducing a keratin 12-positive corneal epithelioid cell from a surface ectoderm-derived cell. More specifically, the present invention relates to a method for inducing a keratin 12-positive corneal epithelioid cell, comprising introducing PAX6, KLF4, and OCT4 into a surface ectoderm-derived cell, such as an oral mucosal epithelial cell, and a corneal epithelioid cell induced by the method.

Claims

1. A method for producing a corneal epithelial cell, comprising introducing PAX6, KLF4, and OCT4 into a surface ectoderm-derived cell to induce a keratin 12-positive corneal epithelioid cell.

2. The method according to claim 1, wherein the corneal epithelioid cell is induced not through a state of a pluripotent cell.

3. The method according to claim 1, wherein the surface ectoderm-derived cell is an oral mucosal epithelial cell.

4. The method according to claim 1, wherein the corneal epithelioid cell is further keratin 3-positive.

5. The method according to claim 4, wherein two PAX6 isoforms, Pa and Pb, are both introduced.

6. The method according to claim 1, wherein PAX6, KLF4, and OCT4 are introduced using one virus vector.

7. A method for producing a corneal epithelioid cell sheet, comprising producing corneal epithelioid cells by the method according to claim 1 and stratifying the cells.

8. A keratin 12-positive corneal epithelioid cell directly induced from a surface ectoderm-derived cell.

9. The corneal epithelioid cell according to claim 8, wherein the corneal epithelioid cell is further keratin 3-positive.

10. The corneal epithelioid cell according to claim 8, wherein the surface ectoderm-derived cell is an oral mucosal epithelial cell.

11. The corneal epithelioid cell according to claim 10, obtained by introducing PAX6, KLF4, and OCT4 into the surface ectoderm-derived cell.

12. A corneal epithelioid cell sheet prepared by stratifying the cells according to claim 8.