Corneal Epithelial Sheet and Process for Producing the Same

• US 20080026030A1
• Filed: 06/21/2005
• Published: 01/31/2008
• Est. Priority Date: 06/30/2004
• Status: Abandoned Application

• Current Assignee: Arblast USA Inc., Shigeru Kinoshita
• Original Assignee: ArBlast Co., Ltd., Kinoshita
• Inventors: Nakamura, Takahiro, Kinoshita, Shigeru
• Application Number:
  US11/631,258
• Publication Number:
  US 20080026030A1
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61L 27/3813 Epithelial cells, e.g. keratinocytes, urothelial cells
• CPC Class Codes: A61L 27/3891 as distinct cell layers
• CPC Class Codes: C12N 2501/01 Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/33 Insulin
• CPC Class Codes: C12N 2502/097 oral mucosa cells
• CPC Class Codes: C12N 2533/92 Amnion; Decellularised dermis or mucosa
• CPC Class Codes: C12N 5/0621 Eye cells, e.g. cornea, iris pigmented cells photoreceptors C12N5/062

Abstract

A corneal epithelial sheet having a cell layer similar to the anterior epithelium of cornea. A corneal epithelial sheet is obtained through the step (a) of separately preparing a first cell being a self cell and a second cell whose origin is different from that of the first cell, the step (b) of planting the first cell and the second cell on a collagen layer and culturing them, and the step (c) of after proliferation of the cell and second cell resulting in formation of a cell layer, bringing the outermost stratum of the cell layer into contact with the air.

Claims

1. A corneal epithelial sheet comprising:

a cell layer including a first cell that is an autologous cell and a second cell whose origin is different from the first cell, the first cell and the second cell being layered.

2. The corneal epithelial sheet according to claim 1, wherein

the first cell is at least one autologous cell selected from the group consisting of a cell derived from oral mucosal epithelium, a cell derived from conjunctival epithelium, a cell derived from nasal mucosal epithelium, and a cell derived from other mucosal epithelium, as well as a cell derived from an undifferentiated cell capable of constructing any of the mucosal epitheliums;

and

the second cell is at least one cell selected from the group consisting of a cell derived from corneal epithelium, a cell derived from conjunctival epithelium, and a cell derived from amniotic membrane epithelium.

3. The corneal epithelial sheet according to claim 2, wherein the first cell is a cell derived from oral mucosal epithelium.

4. The corneal epithelial sheet according to claim 2, wherein the second cell is a cell of another individual.

5. The corneal epithelial sheet according to claim 2, wherein the second cell is a cell derived from corneal epithelium or a cell derived from amniotic membrane epithelium.

6. The corneal epithelial sheet according to claim 1, further comprising a collagen layer, wherein the cell layer is formed on the collagen layer.

7. The corneal epithelial sheet according to claim 6, wherein the collagen layer is derived from amniotic membrane or amniotic membrane from which the epithelium has been removed.

8. The corneal epithelial sheet according to claim 1, wherein the cell layer comprises at least one of the following properties or characteristics;

cells of the outermost layer are not cornified;

cells of the outermost layer are flat-shaped; and

a barrier function is provided.

9. A process for producing a corneal epithelial sheet, comprising the following steps of:

a) separately preparing a first cell being an autologous cell and a second cell whose origin is different from that of the first cell;

b) seeding the first cell and the second cell on a collagen layer and culturing them; and

c) after proliferation of the first cell and second cell resulting in formation of a cell layer, bringing the surface of the cell layer into contact with the air.

10. The process according to claim 9, wherein

the first cell is at least one autologous cell selected from the group consisting of an oral mucosal epithelial cell, a conjunctival epithelial cell, a nasal mucosal epithelial cell, and other mucosal epithelial cell, as well as an undifferentiated cell capable of constructing any of the mucosal epitheliums;

and

the second cell is at least one cell selected from the group consisting of a corneal epithelial cell, a conjunctival epithelial cell, and an amniotic membrane epithelial cell.

11. The process according to claim 10, wherein the first cell is an oral mucosal epithelial cell.

12. The process according to claim 10, wherein the second cell is a cell of another individual.

13. The process according to claim 10, wherein the second cell is a corneal epithelial cell or an amniotic membrane epithelial cell.

14. The process according to claim 9, wherein the step b is carried out under any of conditions, in coexistence of supporting cells;

and

2) in coexistence of supporting cells and in a state in which an isolation membrane with a pore size through which the supporting cell cannot pass exists between the supporting cells and the collagen layer.

15. The process according to claim 9, wherein the collagen layer is derived from amniotic membrane or amniotic membrane from which the epithelium has been removed.