Cell therapy and neural stimulation for cardiac repair

• US 20060190044A1
• Filed: 02/22/2005
• Published: 08/24/2006
• Est. Priority Date: 02/22/2005
• Status: Active Grant

• Current Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Original Assignee: Cardiac Pacemakers Incorporated (Boston Scientific Corporation)
• Inventors: Girouard, Steven D., Libbus, Imad, Ross, Jeffrey
• Granted Patent: US 7,548,780 B2
• Time in Patent Office: Days
• US Class Current: 607/3
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362
• CPC Class Codes: A61N 1/3629 in combination with non-electric therapy

Abstract

A method and system to enhance cell, gene and/or cytokine therapy for cardiac repair in a mammal.

Claims

1. A method, comprising:

applying electrical stimulation to an efferent parasympathetic nerve which innervates cardiac tissue including one or more cardiac fat pads in a mammal with impaired cardiac function and subjected to exogenous cell therapy comprising donor cells, gene therapy and/or cytokine therapy, in an amount effective to modulate cardiac function.

2. The method of claim 1 further comprising applying electrical therapy to cardiac tissue.

3. The method of claim 2 wherein the electrical therapy is pacing therapy.

4. The method of claim 2 wherein the electrical therapy is cardiac resynchronization therapy (CRT).

5. The method of claim 3 wherein the electrical therapy is cardioversion/defibrillation shocks.

6. The method of claim 1 wherein the efferent nerve is the vagus nerve, carotid sinus nerve or aortic nerve.

7. The method of claim 1 wherein the vagus nerve is electrically stimulated.

8. The method of claim 1 wherein one or more cardiac fat pads are electrically stimulated.

9. The method of claim 1 wherein the donor cells are stem cells.

10. The method of claim 1 wherein the donor cells are hematopoietic stem cells, bone marrow derived stem cells, neural stem cells, SP cells, bone marrow cells or skeletal myoblasts.

11. The method of claim 1 wherein the donor cells are cultured in vitro prior to subjecting the mammal to cell therapy.

12. The method of claim 1 wherein the donor cells include autologous or allogeneic cells.

13. The method of claim 11 or 12 wherein the donor cells are subjected to hypoxic conditions in vitro prior to implantation.

14. The method of claim 1 wherein the donor cells are genetically modified donor cells.

15. The method of claim 1 wherein the cytokine therapy enhances cell localization and/or proliferation in cardiac tissue.

16. The method of claim 1 wherein the electrical stimulation is provided by a neural stimulation device.

17. The method of claim 16 wherein the stimulation is about 5 to 10 second bursts at burst intervals ranging from approximately 1 burst every 30 seconds to 25 approximately 1 burst every 60 seconds at about a frequency of 5 to 150 Hz.

18. The method of claim 1 wherein the electrical stimulation is provided by a neural stimulation lead connected to a cardiac rhythm management (CRM) device.

19. The method of claim 18 wherein the neural stimulation lead is in a vessel proximal to the neural stimulation site.

20. The method of claim 19 wherein the stimulation is about 5 to 10 second bursts at burst intervals ranging from approximately 1 burst every 30 seconds to approximately 1 burst every 60 seconds at about a frequency of 5 to 150 Hz.

21. The method of claim 20 wherein the CRM comprises a sensor to sense a physiological parameter for cardiac function and to provide a signal indicative of the physiological signal.

22. The method of claim 1 further comprising administering an agent that enhances stem cell localization, survival, proliferation, differentiation, or function in cardiac tissue.

23. The method of claim 1 further comprising administering an agent that enhances cardiac function or angiogenesis.

24. The method of claim 1 wherein the electrical stimulation is applied in response to impaired cardiac function.

38. The method of claim 1 or 25 further comprising administering a drug.

25. A method, comprising:

applying electrical therapy using a lead to an efferent parasympathetic nerve which innervates cardiac tissue including one or more cardiac fat pads of a mammal subjected to exogenous cell therapy comprising donor cells, gene therapy and/or cytokine therapy;

sensing a physiologic parameter indicative of cardiac contractility, inflammation, mechanical remodeling, and/or mechanical loading; and

modifying the electrical therapy based on the sensed physiological parameter.

26. The method of claim 25 wherein the lead emerges from an implantable device, the method further comprising pacing the heart using the lead.

27. The method of claim 26 wherein the lead emerges from an implantable device, the method further comprising pacing the heart using a second lead from the implantable device.

28. The method of claim 25 wherein modifying the therapy includes modulating an amplitude of a stimulation signal.

29. The method of claim 25 wherein modifying the therapy includes modulating a frequency of a stimulation signal.

30. The method of claim 25 wherein modifying the therapy includes modulating a burst frequency of a stimulation signal.

31. The method of claim 25 wherein modifying the therapy includes modulating a duration of a stimulation signal.

32. The method of claim 25 further comprising applying electrical therapy to cardiac tissue.

33. The method of claim 32 wherein the electrical therapy is pacing therapy.

34. The method of claim 32 wherein the electrical therapy is cardiac resynchronization therapy (CRT).

35. The method of claim 32 wherein the electrical therapy is cardioversion/defibrillation shocks.

36. The method of claim 25 wherein electrical therapy is applied to the vagus nerve, carotid sinus nerve, aortic nerve, or cardiac fat pads.

37. The method of claim 25 wherein the donor cells are stem cells.