METHODS FOR USING A THREE-DIMENSIONAL STROMAL TISSUE TO PROMOTE ANGIOGENESIS

• US 20030007954A1
• Filed: 10/01/1999
• Published: 01/09/2003
• Est. Priority Date: 04/12/1999
• Status: Abandoned Application

• Current Assignee: Advanced Tissue Sciences, Inc., Theregen, Inc.
• Original Assignee: Theregen, Inc.
• Inventors: ZELTINGER, JOAN, NAUGHTON, GAIL K., MANSBRIDGE, JONATHAN NOEL, PINNEY, ROBERT EMMETT
• Application Number:
  US09/411,585
• Publication Number:
  US 20030007954A1
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/3826 Muscle cells, e.g. smooth muscle cells
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3886 comprising two or more cell types
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention relates to a method for promoting blood vessel formation in tissues and organs. In particular, the method relates to implantation or attachment of an engineered three-dimensional stromal tissue to promote endothelialization and angiogenesis in the heart and related tissues. The three-dimensional stromal tissue of the present invention may be used in a variety of applications including, but not limited to, promoting repair of and regeneration of damaged cardiac muscle, promoting vascularization and healing during cardiac surgery, promoting blood vessel formation at anastomosis sites, and promoting vascularization and repair of damaged skeletal muscle, smooth muscle or connective tissue.

Claims

1. A method for promoting angiogenesis in the heart of a subject, comprising attaching a three-dimensional stromal tissue to the heart of the subject to increase the number of blood vessels in the heart, said stromal tissue comprises stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.

2. The method of claim 1 wherein the three-dimensional stromal tissue is living.

3. The method of claim 1 wherein the stromal cells are fibroblasts, smooth muscle cells, cardiac muscle cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adiposites, or any combination thereof.

4. The method of claim 3 wherein the smooth muscle cells are aortic smooth muscle cells.

5. The method of claim 1 wherein the framework is composed of a biodegradable material.

6. The method of claim 5 wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, collagen gel or dextran.

7. The method of claim 1 wherein the framework is composed of a non-biodegradable material.

8. The method of claim 7 wherein the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene or a nitrocellulose compound.

9. The method of claim 1 wherein the framework is a mesh.

10. The method of claim 1 wherein the stromal tissue is obtained directly from a fresh culture.

11. The method of claim 1 wherein the stromal tissue has been cryopreserved.

12. The method of claim 1 wherein the stromal tissue is adhered to the heart by natural cellular attachment.

13. The method of claim 1 wherein the stromal tissue is attached to the heart by an attachment means.

14. The method of claim 13 wherein the attachment means is a suture, a biologic glue, a synthetic glue, a laser dye or a hydrogel.

15. The method of claim 14 wherein the biologic glue is a fibrin glue.

16. The method of claim 1, wherein the stromal tissue is attached to the heart epicardium.

17. The method of claim 1 wherein the stromal tissue is attached to the heart myocardium.

18. The method of claim 1 in which the stromal tissue is attached to the heart endocardium.

20. The method of claim 19, wherein the mammalian tissue is cardiac tissue, skeletal muscle, smooth muscle, connective tissue or skin tissue.

21. The method of claim 19 wherein the stromal cells are fibroblasts, smooth muscle cells, cardiac muscle cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adiposites, or any combination thereof.

22. The method of claim 19 wherein the framework is composed of a biodegradable material.

23. The method of claim 22 wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, collagen gel or dextran.

24. The method of claim 19 wherein the framework is composed of a non-biodegradable material.

25. The method of claim 24 wherein the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene or a nitrocellulose compound.

26. The method of claim 19 wherein the framework is a mesh.

27. The method of claim 19 wherein the stromal tissue is obtained directly from a fresh culture.

28. The method of claim 19 wherein the stromal tissue has been cryopreserved.

29. The method of claim 19 wherein the stromal tissue is adhered to the mammalian tissue by natural cellular attachment.

30. The method of claim 29 wherein the stromal tissue is attached to the mammalian tissue by an attachment means.

31. The method of claim 30 wherein the attachment means is a suture, a biologic glue, a synthetic glue, a laser dye or a hydrogel.

19. A method for promoting vascularization of a mammalian tissue in vivo, comprising attaching a three-dimensional stromal tissue to the mammalian tissue to increase the number of blood vessels in the mammalian tissue, said stromal tissue comprising stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.

32. A method for promoting healing of a site of anastomosis in a subject, comprising attaching a three-dimensional stromal tissue to the site to promote growth of endothelial cells and increase the number of blood vessels in the site, wherein said stromal tissue comprises stromal cells and connective tissue proteins naturally secreted by the stromal cells attached to and substantially enveloping a framework composed of a biocompatible, non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells.

33. The method of claim 32, wherein the step of attaching comprises wrapping a three-dimensional stromal tissue around the site of anastomosis to promote endothelialization of the site.

34. The method of claim 32, wherein the stromal cells are fibroblasts, smooth muscle cells, cardiac muscle cells, endothelial cells, pericytes, macrophages, monocytes, leukocytes, plasma cells, mast cells, adiposites or any combination thereof.

35. The method of claim 32 wherein the framework is composed of a biodegradable material.

36. The method of claim 35 wherein the biodegradable material is cotton, polyglycolic acid, cat gut sutures, cellulose, gelatin, collagen gel or dextran.

37. The method of claim 32 wherein the framework is composed of a non-biodegradable material.

38. The method of claim 37 wherein the non-biodegradable material is a polyamide, a polyester, a polystyrene, a polypropylene, a polyacrylate, a polyvinyl, a polycarbonate, a polytetrafluorethylene or a nitrocellulose compound.

39. The method of claim 32 wherein the framework is a mesh.

40. The method of claim 32 wherein the stromal tissue is adhered to the site by natural cellular attachment.

41. The method of claim 32 wherein the stromal tissue is attached to the site by any of a suture, a biologic glue, a synthetic glue, a laser dye, or a hydrogel.