IP Library Granted Patent US 8,124,071
Granted Patent B2
US 8,124,071 · App. 12/325,373 · Granted Feb 28, 2012

Methods of reducing transplant rejection and cardiac allograft vasculopathy by implanting autologous stem cells

Assignee: New York Medical College
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Quick Facts
Patent No.
US 8,124,071
App. No.
12/325,373
Granted
Feb 28, 2012
Kind
B2
Abstract

The invention provides novel methods of reducing transplant rejection and cardiac allograft vasculopathy in humans by employing the implantation of autologous progenitor cells into the transplanted donor heart. The autologous progenitor cells can be vascular progenitor cells (VPCs) and/or myocyte progenitor cells (MPCs) isolated from the recipient's explanted heart. Alternatively, bone marrow progenitor cells (BMPCs) isolated from the recipient may also be used.

Claims (23)

1. A method of reducing an immune response to a transplanted donor heart in a recipient subject comprising

administering isolated adult cardiac progenitor cells to the transplanted donor heart, wherein said adult cardiac progenitor cells are isolated from the recipient subject's myocardial tissue and are lineage negative and c-kit positive, and wherein said cardiac progenitor cells generate immunocompatible myocardium and immunocompatible myocardial vessels following their administration, thereby reducing the immune response to said transplanted donor heart.

2. The method of claim 1 , wherein prior to administration, said cardiac progenitor cells are separated into vascular progenitor cells and myocyte progenitor cells, wherein said vascular progenitor cells and said myocyte progenitor cells are each expanded in culture to obtain pure cultures of each of said vascular progenitor cells and said myocyte progenitor cells, and each are subsequently administered to said transplanted donor heart, wherein said vascular progenitor cells are vascular endothelial growth factor receptor 2 (VEGFR2) positive and differentiate into immunocompatible endothelial cells and smooth muscle cells, and wherein said myocyte progenitor cells are VEGFR2 negative and differentiate into immunocompatible cardiomyoctyes.

3. The method of claim 1 , further comprising exposing the cardiac progenitor cells to one or more cytokines prior to administration.

4. The method of claim 3 , wherein said cardiac progenitor cells are activated by exposing the cells to one or more cytokines.

5. The method of claim 1 , wherein said subject is human.

6. The method of claim 1 , further comprising administering to the subject an immunosuppressive therapy.

7. A method of reducing an immune response to a transplanted donor heart in a recipient subject comprising

administering isolated myocyte progenitor cells to the transplanted donor heart, wherein said myocyte progenitor cells are isolated from the recipient subject's myocardial tissue and are lineage negative, c-kit positive, and VEGFR2 negative, and wherein said myocyte progenitor cells generate immunocompatible myocardium following their administration, thereby reducing the immune response to said transplanted donor heart.

8. The method of claim 7 , wherein said myocyte progenitor cells differentiate into immunocompatible cardiomyocytes.

9. The method of claim 7 , further comprising administering to the subject an immunosuppressive therapy.

10. A method of reducing cardiac allograft vasculopathy in a subject who has received a transplanted donor heart comprising

administering isolated vascular progenitor cells to the transplanted donor heart, wherein said vascular progenitor cells are isolated from the recipient subject's myocardial tissue and are lineage negative, c-kit positive, and VEGFR2 positive, and wherein said vascular progenitor cells generate immunocompatible coronary vasculature, thereby repairing/and or regenerating the non-immunocompatible coronary arteries of the donor heart.

11. The method of claim 10 , wherein said vascular progenitor cells differentiate into immunocompatible endothelial cells and smooth muscle cells.

12. The method of claim 10 , further comprising administering to the subject an immunosuppressive therapy.

13. The method of claim 1 , wherein said cardiac progenitor cells are expanded in culture prior to administration to the donor heart.

14. The method of claim 7 , wherein said myocyte progenitor cells are expanded in culture prior to administration to the donor heart.

15. The method of claim 10 , wherein said vascular progenitor cells are expanded in culture prior to administration to the donor heart.

16. The method of claim 1 , wherein said adult cardiac progenitor cells are administered to the transplanted donor heart by intramyocardial or intracoronary injection.

17. The method of claim 7 , wherein said myocyte progenitor cells are administered to the transplanted donor heart by intramyocardial or intracoronary injection.

18. The method of claim 10 , wherein said vascular progenitor cells are administered to the transplanted donor heart by intramyocardial or intracoronary injection.

19. The method of claim 2 , wherein said pure vascular progenitor cells are administered simultaneously with said pure myocyte progenitor cells.

20. The method of claim 2 , wherein said pure vascular progenitor cells are administered after administration of said pure myocyte progenitor cells.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 2, 2009
From: ANVERSA, PIERO, DR.; LERI, ANNAROSA, DR.; KAJSTURA, JAN, DR.
To: NEW YORK MEDICAL COLLEGE
Reel/Frame 022189/0592 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2009
From: ANVERSA, PIERO, DR.; LERI, ANNAROSA, DR.; KAJSTURA, JAN, DR.
To: NEW YORK MEDICAL COLLEGE
Reel/Frame 022089/0001 →
LICENSE Recorded Jan 12, 2009
From: NEW YORK MEDICAL COLLEGE
To: AUTOLOGOUS REGENERATION, LLC
Reel/Frame 022089/0073 →
Continuity (2)
Provisional Application 60991499 · Nov 30, 2007
Related Publication 20090169525A1 · Jul 2, 2009