Device having a microporous membrane lined deformable wall for implanting cell cultures

• US 6,479,066 B1
• Filed: 12/16/1999
• Issued: 11/12/2002
• Est. Priority Date: 12/16/1999
• Status: Expired due to Fees

• Current Assignee: RST Implanted Cell Technology, Inc.
• Original Assignee: RST Implanted Cell Technology, Inc.
• Inventors: Harpstead, Stanley D.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/464,560
• Time in Patent Office: 1,062 Days
• Field of Search: 424/93.7, 424/422, 424/423, 424/424, 435/177, 435/180, 435/182, 435/39.5, 435/402, 435/289.1, 435/366, 435/382, 623/11
• US Class Current: 424/424
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells

Abstract

A device and method of using the device are provided for implanting cell cultures in a host. The device is formed of a deformable body, a microporous membrane and a sealable port. The shape of the body which is preferably rounded can be altered by applying stress or pressure, The body comprises a continuous wall constructed of a mesh material, and the membrane lines a surface of the body. The wall and membrane define an enclosed three-dimensional cavity for containing a cell culture. Openings of the membrane allow for passage of therapeutic substances produced by the cells and nutrients or biomolecules produced by host. The sealable port is configured for adding a cell culture to the cavity, and is formed of a material that is capable of resealing after being punctured with a needle. Because the device is deformable, it can be compressed and placed in an implantation site where it expands to conform to contours of tissue surrounding the site. The mesh may be formed of spring tempered stainless steal or memory metals. The membrane may be coated with a material such as extracellular matrix material that facilitates attachment of cells such as by ionic or covalent bonding. An external surface of the device may be coated with an angiogenic material.

Claims

1. A device for implanting a cell culture in a host, comprising:

a. a biocompatible deformable body whose shape can be altered by applying stress or pressure, said body comprising a continuous wall constructed from a mesh material,

b. a biocompatible microporoas membrane lining a surface of the deformable body, wherein the continuous wall and biocompatible microporous membrane define an enclosed three-dimensional cavity; and

c. a sealable port adapted and configured for adding a cell culture to the enclosed three-dimensional cavity, wherein the sealable port is formed of a material that is capable of resealing after being punctured with a needle.

2. The device of claim 1, wherein the deformable body is formed from a material selected from the group consisting of stainless steel and memory metals.

3. The device of claim 1, further comprising a coating material covering a surface of the microporous membrane that is proximate the cavity.

4. The device of claim 3, wherein the coating material is a biologically active material.

5. The device of claim 4, wherein the biologically active material-is attached to the membrane by ionic or covalent bonding.

6. The device of claim 5, wherein the biologically active material facilitates attachment of cells to the microporous membrane.

7. The device of claim 5, wherein the biologically active material is an extracellular matrix molecule.

8. The device of claim 7, wherein the extracellular matrix molecule is selected from the group consisting of laminin, tenascin, collagen, netrin, semaphorin, thrombospondin, fibronectin, vitronectin, proteoglycan and biologically active fragments thereof.

9. The device of claim 8, wherein the biologically active fragment includes a extracellular matrix binding sequence.

10. The device of claim 5, wherein the biologically active material includes cell-cell adhesion molecules.

11. The device of claim 10, wherein the cell-cell adhesion molecule is selected from the group consisting of caherin superfamily and immunoglobulin (Ig) superfamily molecules.

12. The device of claim 1, wherein the microporous membrane comprises a microporous polymeric material.

13. The device of claim 1, wherein the microporous polymeric material is selected from the group consisting of linear polyesters of carbonic acid, poly(vinylchloride), polyamides, styrene-acrylic acid copolymers, polysulfones, halogenated poly(vinylidene), polychloroethers, poly(urethanes) and poly(imides).

14. The device of claim 1, wherein the microporous membrane lines an interior surface of the deformable body.

15. The device of claim 1, wherein the microporous membrane lines an external surface of the deformable body.

16. The device of claim 1, wherein the deformable body is a cylinder, sphere or ovoid.

17. The device of claim 1, wherein the sealable port is formed from a material selected from the group consisting of silicone and polyurethane.

18. The device of claim 17, wherein the sealable port includes silicone and is maintained under pressure.

19. The device of claim 1, further comprising means for preventing- a needle from penetrating the microporous membrane.

20. The device of claim 1, wherein the cell culture includes a mammalian cell culture selected from the group consisting of human epithelial cells (HeLa), human embryonic kidney cells (HEK), and Chinese hamster ovary cells (COS).

21. The device of claim 1, wherein the cell culture includes cells that are genetically modified.

22. The device of claim 21, wherein the cells are genetically modified to present a complementary cell-cell adhesion molecule on their plasma membrane.

23. The device of claim 1, wherein cells in the cell culture are activated upon binding to the microporous membrane, said activation resulting in release of vesicle contents, increase in transcription of a desired gene, increase in translation of MRNA, facilitation of post-translational splicing, increase in vesicle loading or facilitation of vesicle positioning or processing to a desired gene product.

24. The device of claim 23, wherein activation of the cells occurs due to activation of cell adhesion molecules expressed on a plasma membrane of the cell.