Cardiac valve replacement

• US 6,652,583 B2
• Filed: 04/09/2001
• Issued: 11/25/2003
• Est. Priority Date: 04/07/2000
• Status: Expired due to Fees

• Current Assignee: Rhode Island Hospital
• Original Assignee: Rhode Island Hospital
• Inventors: Hopkins, Richard A., Hoffman-Kim, Diane
• Primary Examiner(s): Willse, David H.
• Assistant Examiner(s): Blanco, Javier G.
• Application Number:
  US09/828,768
• Publication Number:
  US 20010051824A1
• Time in Patent Office: 960 Days
• Field of Search: 623/2-2-, 623/1.24, 623/1.26, 623/917, 623/918, 623/925
• 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, isolated myofibroblasts, and isolated endothelial cells, 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. The valve of claim 1, wherein an external layer of said valve comprises a monolayer of said endothelial cells and wherein an inner layer comprises said isolated myofibroblasts.

7. The valve of claim 5, wherein less than 20% of total collagen production by said myofibroblast is type III collagen.

8. The valve of claim 5, wherein less than 15% of total collagen production by said myofibroblast is type III collagen.

9. The valve of claim 5, wherein said myofibroblast is derived from mammalian heart leaflet interstitial tissue.

10. The valve of claim 5, wherein said myofibroblasts is derived from a mammalian vascular or dermal tissue.

11. The valve of claim 5, wherein said myofibroblasts is derived from human heart leaflet interstitial tissue.

12. The valve of claim 5, wherein an external layer of said valve comprises a monolayer of said endothelial cells and wherein an inner layer comprises said isolated myofibroblasts.

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

13. A bioprosthetic heart valve comprising isolated myofibroblasts, wherein said myofibroblasts are genetically altered to increase type I collagen production relative to type III collagen production.