Method of reducing glial scar formation and promoting axon and blood vessel growth and/or regeneration through the use of activated immature astrocytes

• US 4,900,553 A
• Filed: 09/11/1987
• Issued: 02/13/1990
• Est. Priority Date: 09/11/1987
• Status: Expired due to Term

• Current Assignee: Case Western Reserve University
• Original Assignee: Case Western Reserve University
• Inventors: Silver, Jerry, Smith, George M., Jacobberger, James W.
• Primary Examiner(s): Page, Thurman K.
• Application Number:
  US07/096,373
• Time in Patent Office: 886 Days
• Field of Search: 435/174, 435/176, 435/179, 435/177, 435/240.241, 435/240.242, 435/240.243, 435/240, 435/246, 935/12, 424/93, 424/422, 424/423
• US Class Current: 424/423
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12N 2510/00 Genetically modified cells

Abstract

The present invention relates to "activated" immature astrocytes and methods of utilizing the activated immature astrocytes to reduce secondary necrosis and scar formation in central nervous system tissue as well as to promote axon and/or blood vessel growth or regeneration. In specific embodiments of the invention, activated immature astrocytes are used in injectable form or on a polymer implant. The activated immature astrocytes and pharmaceutical compositions comprising same, may be used to treat disorders of the nervous system resulting from accidents or diseases which have in some way damaged the nerve tissue.

Claims

1. A method for promoting directed axon regeneration which comprises the steps of:

(a) providing activated immature astrocytes;

(b) seeding an effective amount of said activated immature astrocytes on to an implant; and

,

(c) inserting said seeded implant near the ends of damaged axons to promote directed axon regeneration.

2. The method of claim 1, wherein said activated immature astrocytes are stellate-shaped, GFAP-positive astrocytes.

3. The method of claim 1, wherein said activated immature astrocytes are embryonic through postnatal day 8 astrocytes.

4. The method of claim 3, wherein said activated immature astrocytes are postnatal day 2 through postnatal day 8 astrocytes.

5. The method of claim 1, wherein said damaged axons are forebrain axons.

6. The method of claim 5, wherein said forebrain axons are commissural axons.

7. The method of claim 1, wherein said damaged axons are spinal axons.

8. The method of claim 7, wherein said spinal axons are sensory axons.

9. The method of claim 1, wherein said implant is nitrocellulose filter paper.

10. The method of claim 9, wherein said nitrocellulose filter paper has a pore size of about 0.45 um.

11. The method of claim 9, wherein said nitrocellulose filter paper has a pore size of about 8.0 um.

12. The method of claim 10, wherein said 0.45 um pore size nitrocellulose filter paper is a 1-mm² home-plate shaped piece of filter paper.

13. The method of claim 11, wherein said 8.0 um pore size nitrocellulose filter paper is a pennant-shaped piece of filter paper.

14. The method of claim 13, wherein said pennant-shaped piece of filter paper is about 3 mm×

.75 mm×

250 um.

15. A method for promoting directed axon regeneration in an animal lacking activated immature astrocytes which comprises the steps of:

(a) providing activated immature astrocytes;

(b) seeding an effective amount of said activated immature astrocytes on to an implant; and

,

(c) inserting said seeded implant into damaged axons of an animal lacking activated immature astrocytes to promote directed axon regeneration.

16. The method of claim 15, wherein said activated immature astrocytes are stellate-shaped, GFAP-positive astrocytes.

17. The method of claim 15, wherein said activated immature astrocytes are embryonic through postnatal day 8 astrocytes.

18. The method of claim 17, wherein said activated immature astrocytes are postnatal day 2 through postnatal day 8 astrocytes.

19. The method of claim 15, wherein said damaged axons are forebrain axons.

20. The method of claim 19, wherein said forebrain axons are commissural axons.

21. The method of claim 15, wherein said damaged axons are spinal axons.

22. The method of claim 21, wherein said spinal axons are sensory axons.

23. The method of claim 15, wherein said animal lacking activated immature astrocytes is an animal 14 days old or older.

24. The method of claim 15, wherein said implant is nitrocellulose filter paper.

25. The method of claim 24, wherein said nitrocellulose filter paper has a pore size of about 0.45 um.

26. The method of claim 25, wherein said 0.45 um pore size nitrocellulose filter paper is a 1-mm² home-plate shaped piece of filter paper.

27. The method of claim 24, wherein said nitrocellulose filter paper has a pore size of about 8.0 um.

28. The method of claim 27, wherein said 8.0 mm pore size nitrocellulose filter paper is a pennant-shaped piece of filter paper.

29. The method of claim 28, wherein said pennant-shaped piece of filter paper is about 3 mm.×

0.75 mm.×

250 um.

30. A method for reducing glial scar formation in damaged central nervous system tissue comprising the steps of:

(a) providing activated immature astrocytes;

(b) seeding an effective amount of said activated immature astrocytes on to an implant; and

,

(c) inserting said seeded implant into damaged tissue of the central nervous system to reduce glial scar formation.

31. The method of claim 30, wherein said activated immature astrocytes are stellate-shaped, GFAP-positive astrocytes.

32. The method of claim 30, wherein said activated immature astrocytes are embryonic through postnatal day 8 astrocytes.

33. The method of claim 32, wherein said activated immature astrocytes are postnatal day 2 through postnatal day 8 astrocytes.

34. The method of claim 30, wherein said damaged tissue of the central nervous system is a forebrain axon.

35. The method of claim 34, wherein said forebrain axon is a commissural axon.

36. The method of claim 30, wherein said damaged tissue of the central nervous system is a spinal axon.

37. The method of claim 36, wherein said spinal axon is a sensory axon.

38. The method of claim 30, wherein said implant is nitrocellulose filter paper.

39. The method of claim 38, wherein said nitrocellulose filter paper has a pore size of about 0.45 um.

40. The method of claim 39, wherein said 0.45 um pore size nitrocellulose filter paper is a 1-mm² home-plate shaped piece of filter paper.

41. The method of claim 38, wherein said nitrocellulose paper has a pore size of about 8.0 um.

42. The method of claim 41, wherein said 8.0 um pore size nitrocellulose filter paper is a pennant-shaped piece of filter paper.

43. A method for reducing glial scar formation in damaged central nervous system tissue in an animal lacking activated immature astrocytes which comprises the steps of:

(a) providing activated immature astrocytes;

(b) seeding an effective amount of said activated immature astrocytes on to an implant; and

,

(c) inserting said seeded implant into damaged tissue of the central nervous system of an animal lacking activated immature astrocytes to reduce glial scar formation.

44. The method of claim 43, wherein said activated immature astrocytes are stellate-shaped, GFAP-positive astrocytes.

45. The method of claim 43, wherein said activated immature astrocytes are embryonic through postnatal day 8 astrocytes.

46. The method of claim 45, wherein said activated immature astrocytes are postnatal day 2 through postnatal day 8 astrocytes.

47. The method of claim 43, wherein said damaged tissue of the central nervous system is a forebrain axon.

48. The method of claim 47, wherein said forebrain axon is a commissural axons.

49. The method of claim 43, wherein said damaged tissue of the central nervous system is a spinal axon.

50. The method of claim 49, wherein said spinal axon is a sensory axon.

51. The method of claim 43, wherein said animal lacking activated immature astrocytes is an animal 14 days old or older.

52. The method of claim 43, wherein said implant is nitrocellulose filter paper.

53. The method of claim 52, wherein said nitrocellulose filter paper has a pore size of about 0.45 um.

54. The method of claim 53, wherein said 0.45 um pore size nitrocellulose filter paper is a 1-mm² home-plate shaped piece of filter paper.

55. The method of claim 52, wherein said nitrocellulose filter paper has a pore size of about 8.0 um.

56. The method of claim 55, wherein said 8.0 um pore size nitrocellulose filter paper is a pennant-shaped piece of filter paper.

57. The method of claim 56, wherein said pennant-shaped piece of filter paper is about 3 mm.×

0.75 mm.×

250 um.