Differentiation of human mesenchymal stem cells to cardiac progenitor cells that promote cardiac repair

• US 20060198829A1
• Filed: 09/14/2005
• Published: 09/07/2006
• Est. Priority Date: 09/14/2004
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University), The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Potapova, Irina, Brink, Peter R., Gaudette, Glenn, Cohen, Ira S., Rosen, Michael R., Robinson, Richard B.
• Granted Patent: US 8,431,397 B2
• Time in Patent Office: Days
• US Class Current: 424/93.21
• CPC Class Codes: C12N 5/0657 Cardiomyocytes; Heart cells

Abstract

A method for treating a subject afflicted with a cardiac disorder, in vivo, comprises (i) inducing differentiation of a progenitor cell, in vitro, to a cardiogenic cell; and (ii) administering a therapeutically effective amount of the cardiogenic cell of step (i) to the subject, thereby treating the cardiac disorder in the subject. This invention further provides related articles of manufacture and methods.

Claims

1. A method for treating a subject afflicted with a cardiac disorder, in vivo, comprising (i) inducing differentiation of a progenitor cell, in vitro, to a cardiogenic cell;

and (ii) administering a therapeutically effective amount of the cardiogenic cell of step (i) to the subject, thereby treating the cardiac disorder in the subject.

2. The method of claim 1, wherein the progenitor cell of step (i) is a stem cell.

3. The method of claim 2, wherein the stem cell is a human mesenchymal stem cell or hematopoietic stem cell.

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

6. The method of claim 1, wherein the differentiation of step (i) comprises forming an embryoid body cell aggregate of progenitor cells.

7. The method of claim 6, wherein the step of forming an embryoid body cell aggregate comprises altering the external forces on progenitor cells to form the embryoid body or hanging progenitor cells to form the embryoid body.

9. The method of claim 1, wherein the administering of step (ii) comprises the implantation of a patch in the heart of the subject, injection through a catheter, use of microparticles or direct injection through the chest wall.

10. The method of claim 9, wherein the patch is comprised of a urinary bladder membrane scaffold, natural or synthetic scaffold, or pericardium.

17. The method of claim 1, wherein the cardiac disorder is myocardial infarction, cardiomyopathy, congestive heart failure, ventricular septal defect, atrial septal defect, congenital heart defect, ventricular aneurysm, ruptured interventricular septum, ruptured chordae tendineae, perforated mitral valve, perforated tricuspid valve, perforated aortic valve, perforated pulmonic valve, a cardiac disorder which is pediatric in origin, or a cardiac disorder which required ventricular reconstruction.

4. (canceled)

8. (canceled)

11-16. -16. (canceled)

18. A method for treating a subject afflicted with a cardiac disorder, in vivo, comprising (i) inducing differentiation of a progenitor cell, in vitro, to a cell that is destined to be cardiogenic;

and (ii) administering a therapeutically effective amount of the cell of step (i) to the subject, thereby treating the cardiac disorder in the subject.

19. The method of claim 18, wherein the progenitor cell of step (i) is a stem cell.

20. The method of claim 19, wherein the stem cell is a human mesenchymal stem cell or hematopoietic stem cell.

22. The method of claim 18, wherein the subject is a human.

23. The method of claim 18, wherein the differentiation of step (i) comprises forming an embryoid body cell aggregate of progenitor cells.

24. The method of claim 23, wherein the step of forming an embryoid body cell aggregate comprises altering the external forces on progenitor cells to form the embryoid body or hanging progenitor cells to form the embryoid body.

26. The method of claim 18, wherein the administering of step (ii) comprises the implantation of a patch in the heart of the subject, injection through a catheter, use of microparticles or direct injection through the heart wall.

27. The method of claim 26, wherein the patch is comprised of a urinary bladder membrane scaffold, natural or synthetic scaffold, or pericardium.

34. The method of claim 18, wherein the cardiac disorder is myocardial infarction, cardiomyopathy, congestive heart failure, ventricular septal defect, atrial septal defect, congenital heart defect, ventricular aneurysm, ruptured interventricular septum, ruptured chordae tendineae, perforated mitral valve, perforated tricuspid valve, perforated aortic valve, perforated pulmonic valve, a cardiac disorder which is pediatric in origin, or a cardiac disorder which required ventricular reconstruction.

21. (canceled)

25. (canceled)

28-33. -33. (canceled)

35. A method for inducing differentiation of a progenitor cell to a cardiogenic cell, in vitro, comprising forming an embryoid body cell aggregate of progenitor cells.

36. The method of claim 35, wherein the step of forming an embryoid body cell aggregate comprises altering the external forces on the progenitor cells to form the embryoid body, or hanging the progenitor cells to form an embryoid body.

37-54. -54. (canceled)