- Document Number:
20050043260
- Appl. No:
10/828669
- Application Filed:
April 21, 2004
- نبذة مختصرة :
The present invention relates to the fields of cell biology, molecular biology, and medicine. More specifically, the invention is directed to generating cardiomyocyte cells from non-cardiomyocyte cells by enhancing the activation of the Wnt/β-catenin signaling pathway. The cardiomyocyte cells that are generated in the present invention are then used as cardiac disease therapy.
- Inventors:
Schneider, Michael D. (Houston, TX, US); Nakamura, Teruya (Houston, TX, US)
- Assignees:
BAYLOR COLLEGE OF MEDICINE (Houston, TX, US)
- Claim:
1. A method of upregulating expression of a cardiac specific polynucleotide in a cell, comprising the step of delivering a composition that activates Wnt/β-catenin signaling.
- Claim:
2. The method of claim 1, wherein the cell is in a tissue.
- Claim:
3. The method of claim 1, wherein the tissue is in a mammal.
- Claim:
4. The method of claim 3, wherein the mammal is a human.
- Claim:
5. The method of claim 1, wherein said cardiac specific polynucleotide is selected from the group consisting of Nkx2.5, GATA4, MEF2C, Tbx5, CRIPTO, NODAL, and cardiac myosin heavy chain.
- Claim:
6. The method of claim 1, wherein said cell exhibits spontaneous cell beating.
- Claim:
7. The method of claim 1, wherein the composition is a modulator of Wnt.
- Claim:
8. The method of claim 7, wherein the modulator enhances expression of Wnt.
- Claim:
9. The method of claim 7, wherein the modulator enhances activity of Wnt.
- Claim:
10. The method of claim 1, wherein the composition delivers Wnt to the cell.
- Claim:
11. The method of claim 10, wherein Wnt is delivered as a polynucleotide to the cell.
- Claim:
12. The method of claim 1, wherein the composition delivers Wnt as a polypeptide to the cell.
- Claim:
13. The method of claim 1, wherein the composition is a modulator of β-catenin.
- Claim:
14. The method of claim 13, wherein the modulator enhances accumulation of β-catenin.
- Claim:
15. The method of claim 13, wherein the composition inhibits phosphorylation of β-catenin.
- Claim:
16. The method of claim 15, wherein the composition is an inhibitor of glycogen synthase kinase 3β.
- Claim:
17. The method of claim 16, wherein the composition is lithium.
- Claim:
18. A method of upregulating expression of a cardiac specific polynucleotide in a cell, comprising the step of delivering Wnt to the cell.
- Claim:
19. The method of claim 18, wherein said cardiac specific polynucleotide is selected from the group consisting of Nkx2.5, GATA4, MEF2C, Tbx5, CRIPTO, NODAL, and cardiac myosin heavy chain.
- Claim:
20. The method of claim 18, wherein said cell exhibits spontaneous cell beating.
- Claim:
21. The method of claim 18, wherein Wnt is delivered as a polypeptide to the cell.
- Claim:
22. The method of claim 18, wherein Wnt is delivered as a polynucleotide to the cell.
- Claim:
23. The method of claim 22, wherein the polynucleotide is in a vector.
- Claim:
24. The method of claim 23, wherein the vector is a viral vector.
- Claim:
25. The method of claim 23, wherein the vector is a non-viral vector.
- Claim:
26. The method of claim 24, wherein said viral vector is an adenoviral vector, an adeno-associated vector, a retroviral vector or a lentiviral vector.
- Claim:
27. The method of claim 18, wherein the cell is in a tissue.
- Claim:
28. The method of claim 27, wherein the tissue is in a mammal.
- Claim:
29. The method of claim 28, wherein the mammal is a human.
- Claim:
30. A method of enhancing proliferation or differentiation of a cardiomyocyte cell from a non-cardiomyocyte cell, comprising the step of delivering a composition to said non-cardiomyocyte cell that activates Wnt/β-catenin signaling.
- Claim:
31. The method of claim 30, wherein said non-cardiomyocyte cell is derived from autologous tissue.
- Claim:
32. The method of claim 30, wherein said non-cardiomyocyte cell is derived from allogeneic tissue.
- Claim:
33. The method of claim 30, wherein said non-cardiomyocyte cell is derived from xenogeneic tissue.
- Claim:
34. The method of claim 30, wherein said cardiomyocyte cell is defined as a cell comprising at least one of the following: expression of Nkx2.5; expression of GATA4; expression of Tbx5; expression of MEF2C; and expression of cardiac myosin heavy chain.
- Claim:
35. The method of claim 30, wherein said cardiomyocyte cell exhibits spontaneous cell beating.
- Claim:
36. The method of claim 30, wherein said non-cardiomyocyte cell is a fibroblast, a stem cell, a progenitor cell.
- Claim:
37. The method of claim 36, wherein the non-cardiomyocyte is obtained from bone marrow, umbilical cord blood, umbilical tissue, circulating endothelial progenitor cells, cardiac fibroblasts, adipose tissue or skin.
- Claim:
38. A method of treating cardiovascular disease in a subject comprising the step of delivering a composition that activates Wnt/β-catenin signaling to the cell.
- Claim:
39. The method of claim 38, wherein said method is further defined as: obtaining a cell from the subject; delivering the composition to activate Wnt/β-catenin signaling to said cell; growing said cell to form a cell culture; and delivering at least one cell from said cell culture to said subject.
- Claim:
40. The method of claim 39, wherein said delivering at least one cell from said cell culture to said subject is further defined as: generating a tissue from said at least one cell from said cell culture; and administering said tissue to said subject.
- Claim:
41. The method of claim 38, wherein the cardiovascular disease is heart failure.
- Claim:
42. A method of generating myocytes comprising the steps of: obtaining non-cardiomyocyte cells; admixing a composition that activates Wnt/β-catenin signaling; and in vitro differentiating the cells to generate myocytes.
- Claim:
43. The method of claim 43, wherein obtaining said non-cardiomyocyte cells comprises performing a tissue biopsy.
- Claim:
44. The method of claim 43, wherein the tissue is bone marrow, umbilical cord blood, umbilical tissue, circulating endothelial progenitor cells, cardiac fibroblasts, adipose tissue or skin.
- Claim:
45. A method of treating a subject suffering from an infarcted myocardium comprising the step of administering to the subject an effective amount of the myocytes of claim 42, wherein the amount repairs the infarcted myocardium.
- Claim:
46. The method of claim 45, wherein the repairs comprise regeneration of cardiomyocytes.
- Claim:
47. A method of repairing an injured myocardium comprising the step of administering to a subject an effective amount of the myocytes of claim 42, wherein the amount is effective in repairing the injured myocardium.
- Claim:
48. The method of claim 47, wherein repairing comprises at least partially restoring structural integrity to the injured myocardium.
- Claim:
49. The method of claim 47, wherein repairing comprises at least partially restoring functional integrity to the injured myocardium.
- Current U.S. Class:
514044/000
- الرقم المعرف:
edspap.20050043260
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