DIRECT DIFFERENTIATION OF CARDIOMYOCYTES FROM HUMAN EMBRYONIC STEM CELLS
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Abstract
The present invention relates to the induction of differentiation in stem cells to cardiomyocytes and factors such as prostaglandin alone or in combination with other factors including essential minerals selected from the group including transferrin and selenium, small molecules selected from the group including a p38 MAPK inhibitor such as SB203580 and protein growth factors of the FGF, IGF and BMP families such as but not limited to IGF1, FGF2, BMP2, BMP4 and BMP6. and insulin that influence the process of differentiation to cardiomyocytes. Media that is appropriate for the induction of differentiation of cardiomyocytes from stem cells is also provided wherein the media contains these factors. The use of cardiomyocytes and cardiac progenitors produced by the directed differentiation in transplantation and screening for cardiac compounds is also provided.
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Citations
95 Claims
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1-74. -74. (canceled)
- 75. A method of inducing or enhancing cardiomyocyte differentiation of a stem cell, the method comprising culturing the stem cell in the presence of prostacyclin (PGI2), or an analogue or functional equivalent thereof, alone or in combination with an essential mineral, a small molecule or a protein growth factor of the FGF, IGF or BMP family.
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76. A method of inducing or enhancing cardiomyocyte differentiation of a stem cell, the method comprising culturing the stem cell in the presence of a gene product expressed by a gene listed in Table 1.
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77. A method of inducing or enhancing cardiomyocyte differentiation in a stem cell said method comprising culturing the stem cell in a culture medium in which the effect caused by insulin, or an analogue thereof, is reduced.
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90. A conditioned media from a culture of an embryonic cell or a defined media when used to induce or enhance cardiomyocyte differentiation of a stem cell, wherein said media:
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(i) comprises a gene product expressed from a gene listed in Table 1; (ii) comprises PGI2, or an analogue or functional equivalent thereof, alone or in combination with an essential mineral, a small molecule or a protein growth factor of the FGF, IGF or BMP family; (iii) comprises transferrin; (iv) comprises selenium;
or(v) has a reduced amount of insulin, or an analogue thereof. - View Dependent Claims (91)
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Specification