Electroactive materials for stimulation of biological activity of stem cells

• US 6,569,654 B2
• Filed: 01/02/2001
• Issued: 05/27/2003
• Est. Priority Date: 09/18/1998
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Shastri, Venkatram, Rahman, Nahid, Langer, Robert, Martin, Ivan
• Primary Examiner(s): Weber, Jon P.
• Application Number:
  US09/753,407
• Publication Number:
  US 20020034796A1
• Time in Patent Office: 875 Days
• Field of Search: 435/173.8
• US Class Current: 435/173.8
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: Y10S 977/91 Strengthening cell or tissue
• CPC Class Codes: Y10S 977/925 Bioelectrical

Abstract

Compositions, methods and systems are provided for the stimulation of biological activities within stem cells by applying electromagnetic stimulation to an electroactive material, wherein the electromagnetic stimulation is coupled to the electromagnetic material. In general the present invention involves attaching or associating the desired cells to or with a surface comprising an electroactive material, and applying electromagnetic radiation directly to the desired area. In preferred embodiments, the stimulation of biological activities within cells results from inducing one or more activities including, but not limited to, gene expression, cell growth, cell differentiation, signal transduction, membrane permeability, cell division, contraction, and cell signaling. In exemplary embodiments, the electroactive materials used in the present invention are either two-dimensional substrates such as thin films having at least one surface of an electroactive material, or in alternative embodiments, the electroactive materials are three-dimensional substrates comprising a matrix having at least one surface of an electroactive material.

Claims

1. A method for stimulating one or more biological activities within mesenchymal stem cells comprising:

contacting tissue with an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive polymer, and wherein said electroactive polymer has attached thereto, or associated therewith, a matrix incorporating one or more mammalian mesenchymal stem cells; and

applying electromagnetic stimulation at the location of the electroactive substrate, wherein said electromagnetic stimulation is coupled to said electroactive polymer.

2. The method of claim 1, wherein said stimulation of one or more biological activities results from an alteration in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

3. The method of claim 2, wherein said stimulation of one or more biological activities is selected from the group consisting of gene expression, cell growth, cell differentiation, cell death, cell signaling, cell signal transduction, cell contraction and any combination of these biological activities.

4. The method of claim 1, wherein said electromagnetic stimulation is coupled to said electroactive polymer by physical contact.

5. The method of claim 1, wherein said electromagnetic stimulation is coupled to said electroactive polymer by electromagnetic induction.

6. The method of claim 1, wherein said electroactive substrate is two-dimensional.

7. The method of claim 6, wherein said electroactive substrate comprises one or more thin films of said electroactive polymer.

8. The method of claim 1, wherein said electroactive substrate is three-dimensional.

9. The method of claim 8, wherein the electroactive substrate comprises an electroactive polymer associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, molecular gels, and cellular solids.

10. The method of claim 9, wherein the electroactive polymer is combined with the matrix to form a composite.

11. The method of claim 1, wherein said polymer is conductive.

12. The method of claim 1, wherein said polymer is a semiconductor.

13. The method of claim 1, wherein said polymer is an ionically conducting polymer.

14. The method of claim 1, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyryn), and poly(heme).

15. A tissue engineering method, comprising:

providing a composition of mesenchymal stem cells and an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive polymer, and wherein said mesenchymal stem cells are attached thereto or associated with said electroactive substrate;

applying electromagnetic stimulation to said composition, wherein said electromagnetic stimulation is coupled to said electroactive polymer; and

contacting said composition with a mammalian tissue, wherein the step of contacting may be performed before or after the step of applying.

16. The method of claim 15, wherein said one or more biological activities is selected from the group consisting of gene expression, cell growth, cell differentiation, cell signal transduction, cell signaling, cell contraction and any combination of these biological activities.

17. The method of claim 15, wherein said electromagnetic stimulation is coupled to said electroactive polymer by physical contact.

18. The method of claim 15, wherein said electromagnetic stimulation is coupled to said electroactive polymer by electromagnetic induction.

19. The method of claim 15, wherein said electroactive substrate is two-dimensional.

20. The method of claim 19, wherein said electroactive substrate comprises one or more thin films of said electroactive polymer.

21. The method of claim 15, wherein said electroactive substrate is three-dimensional.

22. The method of wherein claim 21, wherein said electroactive substrate comprises an electroactive polymer associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, molecular gels and cellular solids.

23. The method of claim 22, wherein the electroactive polymer is combined with the matrix to form a composite.

24. The method of claim 15, wherein said polymer is conductive.

25. The method of claim 15, wherein said polymer is a semiconductor.

26. The method of claim 15, wherein said polymer is an ionically conducting polymer.

27. The method of claim 15, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyryn), and poly(heme).

28. A tissue engineering method, comprising:

providing a composition of mesenchymal stem cells and an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive polymer, and wherein said mesenchymal stem cells are attached thereto or associated with said electroactive substrate;

applying electromagnetic stimulation to said composition, wherein said electromagnetic stimulation is coupled to said electroactive polymer;

removing said stimulated cells from said electroactive polymer; and

contacting the stimulated cells with a mammalian tissue.

29. The method of claim 28, wherein said effecting the stimulation of one or more biological activities results from an alternation in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

30. The method of claim 28, wherein said one or more biological activities is selected from the group consisting of gene expression, cell growth, cell differentiation, cell signal transduction, cell signaling, cell contraction and any combination of these biological activities.

31. The method of claim 28, wherein said electromagnetic stimulation is coupled to said electroactive polymer by physical contact.

32. The method of claim 28, wherein said electromagnetic stimulation is coupled to said electroactive polymer by electromagnetic induction.

33. The method of claim 28, wherein said cells comprise.

34. The method of claim 28, wherein said electroactive substrate is two-dimensional.

35. The method of claim 34, wherein said substrate comprises one or more thin films of said electroactive polymer.

36. The method of claim 28, wherein said electroactive substrate is three-dimensional.

37. The method of claim 36, wherein said substrate comprises an electroactive polymer associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, molecular gels, and cellular solids.

38. The method of claim 37, wherein the electroactive polymer is combined with a matrix to form a composite.

39. The method of claim 28, wherein said polymer is conductive.

40. The method of claim 28, wherein said polymer is a semiconductor.

41. The method of claim 28, wherein said polymer is an ionically conducting polymer.

42. The method of claim 28, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyryn), and poly(heme).

43. A tissue engineering method, comprising:

providing a composition of mesenchymal stem cells and an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive polymer, and wherein said mesenchymal stem cells are attached thereto or associated with said electroactive substrate;

contacting said composition with a mammalian tissue; and

applying electromagnetic stimulation to said composition, wherein said electromagnetic stimulation is coupled to said electroactive polymer.

44. The method of claim 43, wherein said effecting the stimulation of one or more biological activities results from an alteration in the cell membrane resting potential, wherein said electroactive substrate is capable of effecting the alteration in the cell membrane resting potential.

45. The method of claim 44, wherein said one or more biological activities is selected from the group consisting of gene expression, cell growth, cell signal transduction, cell differentiation, cell signaling, cell death and any combination of these biological activities.

46. The method of claim 43, wherein said electromagnetic stimulation is coupled to said electroactive polymer by physical contact.

47. The method of claim 43, wherein said electromagnetic stimulation is coupled to said electroactive polymer by electromagnetic induction.

48. The method of claim 43, wherein said electroactive substrate is two-dimensional.

49. The method of claim 48, wherein said electroactive substrate comprises one or more thin films of said electroactive polymer.

50. The method of claim 43, wherein said electroactive substrate is three-dimensional.

51. The method of claim 50, wherein said substrate comprises an electroactive polymer associated with or attached to a matrix, wherein said matrix is selected from the group consisting of polymers, biological polymers, molecular gels and cellular solids.

52. The method of claim 51, wherein the electroactive polymer is combined with the matrix to form a composite.

53. The method of claim 43, wherein said polymer is conductive.

54. The method of claim 43, wherein said polymer is a semiconductor.

55. The method of claim 43, wherein said polymer is an ionically conducting polymer.

56. The method of claim 43, wherein said electroactive polymer is selected from the group consisting of polypyrrole, poly(p-phenylene), poly(p-phenylene-vinylene), poly(thiophene), poly(aniline), poly(porphyryn), and poly(heme).

57. A system for stimulating one or more biological activities of cells comprising:

a composition comprising an electroactive substrate, wherein said electroactive substrate has at least one surface of electroactive polymer, and wherein said electroactive polymer has attached thereto, or associated therewith, one or more mesenchymal stem cells; and

an apparatus for applying electromagnetic energy at the desired location.

58. The system of claim 57, wherein said electroactive substrate is two-dimensional.

59. The system of claim 57, wherein said electroactive substrate is three-dimensional.

60. A two-dimensional stimulant of one or more biological activities comprising one or more films of an electroactive polymer, wherein said one or more films are associated with or attached to one or more mesenchymal stem cells.

61. A three-dimensional stimulant of one or more biological activities comprising an electroactive polymer associated with or attached to a matrix, and wherein said three-dimensional stimulant is associated with or attached to one or more mesenchymal stem cells.