Irreversible electroporation using tissue vasculature to treat aberrant cell masses or create tissue scaffolds

• US 9,867,652 B2
• Filed: 11/23/2011
• Issued: 01/16/2018
• Est. Priority Date: 04/29/2008
• Status: Active Grant

• Current Assignee: Virginia Tech Intellectual Properties, Inc.
• Original Assignee: Virginia Tech Intellectual Properties, Inc.
• Inventors: Sano, Michael B., Davalos, Rafael V., Robertson, John L., Garcia, Paulo A., Neal, II, Robert E.
• Primary Examiner(s): Peffley, Michael
• Assistant Examiner(s): Vahdat, Khadijeh
• Application Number:
  US13/989,175
• Publication Number:
  US 20130253415A1
• Time in Patent Office: 2,246 Days
• Field of Search: 606 33- 51
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61B 2018/1472 for use with liquid electrolyte, e.g. virtual electrodes
• CPC Class Codes: A61B 2218/002 Irrigation
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61M 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The present invention relates to the field of medical treatment of diseases and disorders, as well as the field of biomedical engineering. Embodiments of the invention relate to the delivery of Irreversible Electroporation (IRE) through the vasculature of organs to treat tumors embedded deep within the tissue or organ, or to decellularize organs to produce a scaffold from existing animal tissue with the existing vasculature intact. In particular, methods of administering non-thermal irreversible electroporation (IRE) in vivo are provided for the treatment of tumors located in vascularized tissues and organs. Embodiments of the invention further provide scaffolds and tissues from natural sources created using IRE ex vivo to remove cellular debris, maximize recellularization potential, and minimize foreign body immune response. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.

Claims

1. A method of ablating target tissue cells comprising:

inserting a first device with a first electrode into an artery such that the first electrode is in contact with fluid inside the artery;

inserting a second device with a second electrode into a vein such that the second electrode is in contact with fluid inside the vein;

and

applying electrical energy between the first electrode and the second electrode so as to deliver ablation energy to target tissue cells using the fluid inside the artery and the fluid inside the vein as an electrical conduit.

2. The method of claim 1, wherein the step of applying includes applying electrical energy in an amount sufficient to ablate the target tissue cells by irreversible electroporation (IRE).

3. The method of claim 1, wherein the first electrode is not in contact with the artery or the second electrode is not in contact with the vein.

4. The method of claim 1, wherein the first electrode is in contact with the artery or the second electrode is in contact with the vein.

5. The method of claim 1, wherein the method is performed in vivo.

6. The method of claim 1, wherein the method is performed ex vivo.

7. A method of ablating target tissue cells by irreversible electroporation (IRE) comprising:

inserting a first device with a first electrode into an artery associated with the target tissue cells such that the first device is disposed in the artery and the first electrode is in contact with fluid inside the artery;

inserting a second device with a second electrode into a vein associated with the target tissue cells such that the second device is disposed in the vein and the second electrode is in contact with fluid inside the vein; and

applying a plurality of electrical pulses between the first electrode of the first device disposed in the artery and the second electrode of the second device disposed in the vein so as to deliver ablation energy to the target tissue cells using the fluid inside the artery and the fluid inside the vein as an electrical conduit, the plurality of electrical pulses being sufficient to ablate the target tissue cells by IRE.

8. The method of claim 7, prior to the step of applying a plurality of electrical pulses, further comprising occluding at least one of the artery and the vein to isolate the target tissue cells and preserve existing fluid inside the artery and inside the vein as an electrical conduit.

9. The method of claim 7, prior to the step of applying a plurality of electrical pulses, further comprising:

applying a sine wave voltage signal of varying frequencies through the first electrode of the first device disposed in the artery and the second electrode of the second device disposed in the vein;

determining electrical characteristics of vasculature associated with the target tissue cells based on the applied sine wave voltage signal.

10. The method of claim 7, further comprising perfusing the target tissue cells with a perfusate through vasculature associated with the target tissue cells while the plurality of electrical pulses are being applied.

11. The method of claim 7, further comprising removing cellular debris from a region containing the target tissue cells, thereby creating a tissue scaffold.

12. The method of claim 11, wherein the target tissue cells are from a tissue selected from the group consisting of a heart, a lung, a liver, a kidney, a pancreas, a spleen, a gastrointestinal tract, a urinary bladder, a prostate, an ovary, a brain, an ear, an eye, and skin.

13. The method of claim 11, wherein the tissue scaffold has a thickness in at least one dimension of about 1-10 cm.

14. The method of claim 11, wherein the tissue scaffold comprises a preserved extracellular matrix and preserved vascular structures of a natural tissue source.

15. The method of claim 14, wherein the preserved vascular structures comprise vascular structures involved in macrocirculation.

16. The method of claim 14, wherein the preserved vascular structures comprise vascular structures involved in microcirculation.

17. The method of claim 11, further comprising reseeding the tissue scaffold with living cells under conditions that permit growth of the living cells on or in the tissue scaffold to create an engineered tissue.

18. The method of claim 17, wherein the tissue scaffold is from an animal and the living cells are from a human.

19. The method of claim 17, wherein the engineered tissue is a heart, a lung, a liver, a kidney, a pancreas, a spleen, a gastrointestinal tract, a urinary bladder, a prostate, an ovary, a brain, an ear, an eye, or skin, or a portion thereof.

20. The method of claim 17, wherein the reseeding step is performed in vivo, in vitro, or ex vivo.

21. The method of claim 17, wherein the living cells are autologous, syngenic, isogenic, allogenic, or xenogenic.

22. The method of claim 11, wherein the method is performed in vivo.

23. The method of claim 11, wherein the method is performed ex vivo.

24. The method of claim 11, wherein the cellular debris is removed through one or more chemical techniques, one or more enzymatic techniques, and/or one or more physical techniques.

25. The method of claim 7, further comprising providing, in communication with the artery or the vein, a mechanical perfusion connection device having a one-way valve adapted to electrically isolate the target tissue cells between heart beats and preserve existing fluid inside the artery and inside the vein as an electrical conduit.

26. The method of claim 7, wherein the method is performed in vivo.

27. The method of claim 7, wherein the method is performed ex vivo.

28. A method of ablating target tissue cells comprising:

inserting a first device with a first electrode into an artery and a second device with a second electrode into a vein;

administering fluid into the artery and vein in a manner such that the first and second electrodes are in contact with the fluid; and

applying electrical energy between the first electrode and the second electrode so as to deliver ablation energy to target tissue cells using the fluid as an electrical conduit.

29. The method of claim 28, wherein the method is performed in vivo.

30. The method of claim 28, wherein the method is performed ex vivo.

31. The method of claim 28, wherein the electrode is inserted coaxially into the tubular device.