Neuregulin And Cardiac Stem Cells
The present invention relates to compositions and methods for inducing cardiomyogenesis in mammalian cells, particularly embryonic stem cells in vitro and in vivo.
1 . A method of inducing myocardiogenesis, the method comprising: contacting a mammalian cell with neuregulin, whereby the mammalian cell differentiates into a cell of myocardiac lineage.
2 . The method of claim 1 , wherein the neuregulin is neuregulin 1, neuregulin 2, neuregulin 3 or neuregulin 4.
3 . The method of claim 1 , wherein the neuregulin comprises an EGF like domain.
4 . The method of claim 1 , wherein neuregulin comprises the amino acid sequence of SEQ ID NO:1.
5 . The method of claim 1 wherein said neuregulin is in a pharmaceutically acceptable carrier.
6 . The method of claim 1 , wherein the mammalian cell is in a mammal.
7 . The method of claim 6 , wherein the step of contacting is by intravenous administration of neuregulin to the mammal.
8 . The method of claim 1 , further comprising detecting differentiation of the mammalian cell into a cell of a myocardiac lineage.
9 . The method of claim 8 , whereby differentiation of the mammalian cell into a cell of a myocardiac lineage is detected by detecting expression of a cardiomyocyte marker gene.
10 . The method of claim 8 , whereby differentiation of the mammalian cell into a cell of a myocardiac lineage is detected by detecting expression of a cardiac muscle cell-specific transcription factor.
11 . The method of claim 8 , whereby differentiation of the mammalian cell into a cell of a myocardiac lineage is detected by detecting expression of a cardiac specific gene.
12 . The method of claim 1 , wherein the mammalian cell is an embryonic stem cell.
13 . The method of claim 1 , wherein the mammalian cell is a primate embryonic stem cell.
14 . The method of claim 1 , wherein the mammalian cell is a human embryonic stem cell.
15 . The method of claim 1 , wherein the mammalian cell is further contacted with a cardiomyogenesis enhancing protein.
16 . The method of claim 15 , wherein the cardiomyogenesis enhancing protein is a growth factor involved in cardiomyogenesis.
17 . The method of claim 1 , wherein the mammalian cell is attached to a solid support.
18 . The method of claim 17 , wherein the solid support is a three dimensional matrix.
19 . A method of treating a cardiac muscle disorder, the method comprising: contacting a mammalian cell with neuregulin, whereby the mammalian cell differentiates into a cell of a myocardiac lineage.
20 . The method of claim 19 , wherein the neuregulin is neuregulin 1, neuregulin 2, neuregulin 3 or neuregulin 4.
21 . The method of claim 19 , wherein the neuregulin comprises an EGF like domain.
22 . The method of claim 19 , wherein neuregulin comprises the amino acid sequence of SEQ ID NO:1.
23 . The method of claim 19 , wherein the cardiac muscle disorder is associated with damaged myocardium.
24 . The method of claim 23 , wherein the cardiac muscle disorder is heart failure.
25 . The method of claim 19 , further comprising administering the cell of a myocardiac lineage to an individual with the disorder, thereby treating the disorder.
26 . The method of claim 25 , wherein the administration is by surgical implantation.