Cell substrates and methods of use thereof

• US 20030096408A1
• Filed: 11/13/2002
• Published: 05/22/2003
• Est. Priority Date: 11/16/2001
• Status: Abandoned Application

• Current Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Wang, Jian, Gerber, David A.
• Application Number:
  US10/293,454
• Publication Number:
  US 20030096408A1
• Time in Patent Office: Days
• US Class Current: 435/370
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12N 5/0671 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

A cell support system useful for the implantation of living cells in a subject comprises a solid substrate, typically formed from a biologically inert material. The substrate has a textured surface portion, with the textured surface portion defining a plurality of recessed cavities therein. A plurality of live cells to be implanted are deposited on the textured surface portion so that the cells (or progeny thereof) are protected from mechanical dislodgment.

Claims

1. A cell support useful for the implantation of cells in a subject, said cell support comprising:

a solid substrate formed from a biologically inert material and having a textured surface portion, said textured surface portion defining a plurality of recessed cavities in said textured surface portion; and

a plurality of live cells deposited on said textured surface portion in said recessed cavities so that said cells are protected from mechanical dislodgment therefrom;

wherein said cells consist essentially of nonembryonic hepatic or pancreatic progenitor cells.

2. The cell support according to claim 1, wherein said substrate is substantially flat in shape.

3. The cell support according to claim 1, wherein said substrate is substantially spherical in shape.

4. The cell support according to claim 1, wherein said substrate is comprised of organic material.

5. The cell support according to claim 1, wherein said substrate is comprised of inorganic material.

6. The cell support according to claim 1, wherein said substrate is comprised of silicon.

7. The cell support according to claim 1, wherein said progenitor cells consist essentially of pancreatic progenitor cells.

8. The cell support according to claim 1, wherein said progenitor cells consist essentially of liver progenitor cells.

9. The cell support according to claim 1, wherein said textured surface portion has an area of from about on-half square centimeter up to about 30 square centimeters.

10. The cell support according to claim 1, wherein said textured surface portion is comprised of raised portions and lower portions, with the vertical distance between said raised portions and lowered portions being from about 1 micron to about 50 microns.

11. A method of implanting cells in a subject, comprising the steps of:

(a) providing a cell support comprising (i)a solid substrate formed from a biologically inert material and having a textured surface portion, said textured surface portion defining a plurality of recessed cavities in said textured surface portion, and (ii) a plurality of live cells deposited on said textured surface portion in said recessed cavities so that said cells are protected from mechanical dislodgement therefrom,

wherein said cells consist essentially of nonembryonic hepatic or pancreatic progenitor cells; and

then

(b) implanting said cell support in said subject.

12. The method according to claim 11, wherein said cell support is implanted parenterally in said subject.

13. The method according to claim 11, wherein said cell support is implanted intramuscularly in said subject.

14. The method according to claim 11, wherein said cell support is implanted subcutaneously in said subject.

15. The method according to claim 11, wherein said cell support is implanted intraperitoneally in said subject.

16. The method according to claim 11, wherein said substrate is maintained in said subject for a time sufficient for said cells to proliferate on said surface portion.

17. The method according to claim 11, wherein said subject is afflicted with diabetes, wherein said progenitor cells are pancreatic progenitor cells, and wherein said pancreatic progenitor cells are implanted in said subject in an amount sufficient to treat said diabetes.

18. The method according to claim 11, wherein said substrate is substantially flat in shape.

19. The method according to claim 11, wherein said substrate is substantially spherical in shape.

20. The method according to claim 11, wherein said substrate is comprised of organic material.

21. The method according to claim 11, wherein said substrate is comprised of inorganic material.

22. The method according to claim 11, wherein said substrate is comprised of silicon.

23. The method according to claim 11, wherein said progenitor cells consist essentially of pancreatic progenitor cells.

24. The method according to claim 11, wherein said progenitor cells consist essentially of liver progenitor cells.

25. The method according to claim 11, wherein said textured surface portion has an area of from about on-half square centimeter up to about 30 square centimeters.

26. The method according to claim 11, wherein said textured surface portion is comprised of raised portions and lower portions, with the vertical distance between said raised portions and lowered portions being from about 1 micron to about 50 microns.

27. A method of making a cell support useful for the implantation of living cells in a subject, said method comprising the steps of:

(a) providing a solid substrate formed from a biologically inert material and having a textured surface portion, said textured surface portion defining a plurality of recessed cavities in said textured surface portion; and

then

(b) depositing a plurality of cells on said textured surface portion in said recessed cavities so that said cells are protected from subsequent mechanical dislodgment therefrom, wherein said cells consist essentially of nonembryonic hepatic or pancreatic progenitor cells.

28. The method according to claim 27, wherein said substrate is substantially flat in shape.

29. The method according to claim 27, wherein said substrate is substantially spherical in shape.

30. The method according to claim 27, wherein said substrate is comprised of organic material.

31. The method according to claim 27, wherein said substrate is comprised of inorganic material.

32. The method according to claim 27, wherein said substrate is comprised of silicon.

33. The method according to claim 27, wherein said progenitor cells consist essentially of pancreatic progenitor cells.

34. The method according to claim 27, wherein said progenitor cells consist essentially of liver progenitor cells.

35. The method according to claim 27, wherein said textured surface portion has an area of from about one-half square centimeter up to about 30 square centimeters.

36. The method according to claim 27, wherein said textured surface portion is comprised of raised portions and lowered portions, with the vertical distance between said raised portions and lowered portions being from about 1 micron to about 50 microns.

37. A method for the implantation of cells in a subject, said method comprising the steps of:

(a) providing a solid substrate formed from a biologically inert material and having a textured surface portion, said textured surface portion defining a plurality of recessed cavities in said textured surface portion; and

then

(b) depositing a plurality of live nonembryonic progenitor cells on said textured surface portion in said recessed cavities so that said cells are protected from subsequent mechanical dislodgment therefrom; and

then

(c) implanting said solid support in a subject.

38. The method according to claim 37, further comprising the step of:

(d) maintaining said substrate in said subject for a time sufficient for said cells to proliferate on said surface portion.

39. The method according to claim 38, further comprising the step of

(e) administering a test compound to said subject during said maintaining step.

40. The method according to claim 39, further comprising the step of:

(f) removing said solid support from said subject after said maintaining step.

41. The method according to claim 40, further comprising the step of:

(g) examining said cells to determine the effect of said test compound on said cells.

42. The method of claim 37, wherein said progenitor cells are selected from the group consisting of liver cells, pancreatic cells, intestinal cells, renal cells, and epithelial cells.