Cardiac valve replacement

• US 20010051824A1
• Filed: 04/09/2001
• Published: 12/13/2001
• Est. Priority Date: 04/07/2000
• Status: Active Grant

• Current Assignee: Rhode Island Hospital
• Original Assignee: Rhode Island Hospital
• Inventors: Hopkins, Richard A., Hoffman-Kim, Diane
• Granted Patent: US 6,652,583 B2
• Time in Patent Office: Days
• US Class Current: 623/2.13
• CPC Class Codes: A61F 2/2415 Manufacturing methods
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• 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 27/3843 Connective tissue
• CPC Class Codes: A61L 27/3895 using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062

Abstract

The invention provides a replacement heart valve which contains an acellular matrix as a structural scaffold. The scaffold is seeded with isolated myofibroblasts and/or endothelial cells prior to implantation into a recipient mammal.

Claims

1. A bioprosthetic heart valve comprising an acellular matrix and isolated myofibroblasts wherein at least 60% of the total collagen produced by said myofibroblasts is type I collagen.

2. The valve of

claim 1

, wherein said myofibroblasts produce at least 2-fold greater type I collagen compared to type III collagen.

3. The valve of

claim 1

, wherein said myofibroblasts produce one or more extracellular matrix components selected from the group consisting of fibronectin, elastin, and glycosaminoglycan.

4. The valve of

claim 3

, wherein said glycosaminoglycan is chondroitin sulfate or hyaluronic acid.

5. A valve comprising an acellular matrix and an isolated myofibroblast, wherein less than 25% of total collagen production by said myofibroblast is type III collagen.

6. The valve of

claim 5

, wherein less than 20% of total collagen production by said myofibroblast is type III collagen.

7. The valve of

claim 5

, wherein less than 15% of total collagen production by said myofibroblast is type III collagen.

8. The valve of

claim 5

, wherein said myofibroblast is derived from mammalian heart leaflet interstitial tissue.

9. The valve of

claim 5

, wherein said myofibroblast is derived from a mammalian vascular or dermal tissue.

10. The valve of

claim 5

, wherein said myofibroblast is derived from human heart leaflet interstitial tissue.

11. A method of enhancing production of type I collagen by an isolated myofibroblast, comprising culturing said myofibroblast under pulsatile flow conditions.

12. The method of

claim 11

, wherein said myofibroblast is cultured in the presence of basic fibroblast growth factor.

13. The method of

claim 11

, wherein said myofibroblast is cultured in endothelial cell-conditioned media.

14. The method of

claim 11

, wherein said myofibrobast is cultured in the presence of an isolated endothelial cell.

15. A method of enhancing viability and contractile activity of myofibroblasts in vitro comprising culturing said myofibroblast under pulsatile flow conditions.

16. The method of

claim 15

, wherein said myofibroblast is cultured in endothelial cell-conditioned media.

17. The method of

claim 15

, wherein said myofibrobast is cultured in the presence of an isolated endothelial cell.

18. The method of

claim 15

, wherein said myofibroblast is cultured in the presence of a purified endothelial cell-derived growth factor, wherein said growth factor inhibits apoptosis of said myofibroblast.

19. An isolated myofibroblast, wherein said myofibroblast is genetically altered to increase type I collagen production relative to type III collagen production.

20. A bioprosthetic heart valve comprising the myofibroblast of

claim 19

.

21. A method of manufacturing an artificial heart valve, comprising

(a) providing an acellular matrix,

(b) seeding said matrix with isolated myofibroblasts;

and

(c) culturing said myofibroblasts under pulsatile flow conditions.

22. The method of

claim 21

, wherein said myofibroblasts are derived from an intended recipient from an intended recipient of said centrifugal heart valve.