Materials and Methods for Minimally-Invasive Administration of a Cell-Containing Flowable Composition

• US 20080118561A1
• Filed: 12/06/2005
• Published: 05/22/2008
• Est. Priority Date: 12/08/2004
• Status: Abandoned Application

• Current Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Original Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Inventors: Edelman, Elazer, Nugent, Helen Marie, Bollinger, Steve
• Application Number:
  US11/792,284
• Publication Number:
  US 20080118561A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 27/3808 Endothelial cells
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 Vasodilators for multiple indications
• 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 disclosed invention is based on the discovery that a cell-based therapy can be used to treat, ameliorate, manage and/or reduce the progression of clinical sequelae associated with vascular interventions or cardiovascular diseases, particularly occlusive thrombosis, restenosis, intimal hyperplasia, inflammation and vasodilation. The invention further benefits from the additional discovery that a heretofore undescribed implantable flowable composition is capable of sustaining a confluent population of sufficiently viable cells which can be effectively administered via a minimally-invasive surgical procedure without diminishing the clinical effectiveness or the viability of the cells. The disclosed invention can be used to treat vasculature as well as non-vascular tubular structures such as a fallopian tube.

Claims

1. A flowable composition for treating an injured or diseased site of a tubular anatomical structure wherein said flowable composition comprises a biocompatible matrix and cells and wherein said flowable composition is in an amount effective to treat the injured or diseased site.

2. The flowable composition of claim 1 wherein said cells are endothelial cells or cells having an endothelial-like phenotype.

3. The flowable composition of claim 1 wherein said cells are a co-culture of two or more cells selected from the group consisting of endothelial cells, epithelial cells, smooth muscle cells, fibroblasts, stem cells, endothelial progenitor cells and cardiomyocytes.

4. The flowable composition of claim 1 wherein the flowable composition is shape-retaining.

5. The flowable composition of claim 1 wherein the biocompatible matrix comprises particles or microcarriers.

6. The flowable composition of claim 5 wherein the particles or microcarriers further comprise gelatin, collagen, fibronectin, fibrin, laminin or attachment peptide.

7. The flowable composition of claim 6 wherein the attachment peptide comprises a peptide of sequence arginine-glycine-aspartate (RGD).

8. The flowable composition of claim 5 wherein a particle or microcarrier has a diameter of about 20 microns to about 500 microns.

9. The flowable composition of claim 5 wherein a particle or microcarrier has a diameter of about 200 microns.

10. The flowable composition of claim 1 further comprising cell growth media.

11. The flowable composition of claim 1 wherein said effective amount reduces smooth muscle cell proliferation at the injured or diseased site.

12. The flowable composition of claim 1 wherein said effective amount reduces occlusive thrombosis at the injured or diseased site.

13. The flowable composition of claim 1 wherein said effective amount reduces intimal hyperplasia at the injured or diseased site.

14. The flowable composition of claim 1 wherein said effective amount reduces stenosis or restenosis at the injured or diseased site.

15. The flowable composition of claim 1 wherein said effective amount reduces acute inflammation at the injured or diseased site.

16. The flowable composition of claim 1 wherein said effective amount reduces chronic inflammation at the injured or diseased site.

17. The flowable composition of claim 1 wherein said effective amount reduces vasodilation or vasospasm at the injured or diseased site.

18. The flowable composition of claim 1 wherein said tubular anatomical structure is a blood vessel.

43. The flowable composition of claim 1 wherein said cells are selected from the group consisting of:

a confluent population of cells;

a near-confluent population of cells;

a post-confluent population of cells; and

a population of cells having any one of the foregoing phenotypes.

19. A method of treating an injured or diseased site of a tubular anatomical structure, the method comprising the step of:

contacting with a flowable composition an extraluminal surface of said tubular anatomical structure at or adjacent or in the vicinity of the injured or diseased site of said tubular anatomical structure, wherein said composition comprises a biocompatible matrix and cells and wherein said flowable composition is in an amount effective to treat the injured or diseased site.

20. The method of claim 19 wherein deposition is accomplished by traversing or penetrating an interior wall of said tubular anatomical structure and then depositing the flowable composition on an exterior surface of said tubular anatomical structure at or adjacent or in the vicinity of the injured or diseased site.

21. The method of claim 20 further comprising the step of identifying a site for depositing the flowable composition on an exterior surface of said tubular anatomical structure.

22. The method of claim 21 wherein the identifying step occurs prior to or coincident with the traversing or penetrating step.

23. The method of claim 21 wherein the identifying step is accomplished by imaging.

24. The method of claim 21 wherein the identifying step is accomplished by tactile palpation.

25. The method of claim 19 wherein said contacting step is accomplished by entering the perivascular space by percutaneous administration and then depositing the flowable composition on an exterior surface of said tubular anatomical structure at or adjacent or in the vicinity of the injured or diseased site.

26. The method of claim 25 further comprising the step of identifying a site for depositing the flowable composition on an exterior surface of said tubular anatomical structure.

27. The method of claim 26 wherein the identifying step occurs prior to or coincident with the entering step.

28. The method of claim 26 wherein the identifying step is accomplished by imaging.

29. The method of claim 26 wherein the identifying step is accomplished by tactile palpation.

30. The method of claim 19 wherein the exterior surface of said tubular anatomical structure is a non-luminal surface.

31. The method of claim 19 wherein the exterior surface of said tubular anatomical structure occupies perivascular space.

32. The method of claim 19 wherein said tubular anatomical structure is a blood vessel.

33. The method of claim 32 wherein said blood vessel comprises a stent.

34. The method of claim 33 wherein said injured or diseased site is in the vicinity of the stent.

35. The method of claim 19 wherein said effective amount reduces smooth muscle cell proliferation at the injured or diseased site.

36. The method of claim 19 wherein said effective amount reduces occlusive thrombosis at the injured or diseased site.

37. The method of claim 19 wherein said effective amount reduces intimal hyperplasia at the injured or diseased site.

38. The method of claim 19 wherein said effective amount reduces stenosis or restenosis at the injured or diseased site.

39. The method of claim 19 wherein said effective amount reduces acute inflammation at the injured or diseased site.

40. The method of claim 19 wherein said effective amount reduces chronic inflammation at the injured or diseased site.

41. The method of claim 19 wherein said effective amount reduces vasodilation or vasospasm at the injured or diseased site.

42. The method of claim 19 wherein said tubular anatomical structure is a fallopian tube.