Compositions for regenerating defective or absent myocardium
View Patent ↗Compositions of the invention for regenerating defective or absent myocardium comprise an emulsified or injectable extracellular matrix composition. The composition may also include an extracellular matrix scaffold component of any formulation, and further include added cells, proteins, or other components to optimize the regenerative process and restore cardiac function.
1. An injectable graft composition for myocardial tissue regeneration, comprising acellular heart extracellular matrix (ECM), said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
2. The composition of claim 1 , wherein said composition further comprises an exogenously added cytokine.
3. An injectable graft composition for myocardial tissue regeneration, comprising extracellular matrix (ECM) from a mammalian tissue source comprising acellular small intestine submucosa, said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
4. The composition of claim 3 , wherein said composition further comprises an exogenously added cytokine.
5. An injectable graft composition for myocardial tissue regeneration, comprising extracellular matrix (ECM) from a mammalian tissue source comprising acellular urinary bladder submucosa, said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
6. The composition of claim 5 , wherein said composition further comprises an exogenously added cytokine.
7. An injectable graft composition for myocardial tissue regeneration, comprising extracellular matrix (ECM) from a mammalian tissue source comprising acellular urinary bladder membrane, said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
8. The composition of claim 7 , wherein said composition further comprises an exogenously added cytokine.
9. An injectable graft composition for myocardial tissue regeneration, comprising extracellular matrix (ECM) from a mammalian tissue source comprising acellular liver basement membrane, said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
10. The composition of claim 9 , wherein said composition further comprises an exogenously added cytokine.
11. An injectable graft composition for myocardial tissue regeneration, comprising extracellular matrix (ECM) from a mammalian tissue source comprising acellular stomach submucosa, said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
12. The composition of claim 11 , wherein said composition further comprises an exogenously added cytokine.
13. An injectable graft composition for myocardial tissue regeneration, comprising acellular placental extracellular matrix (ECM), said ECM comprising endogenous glycosaminoglycans (GAGs) convalently linked to said ECM, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added embryonic stem cell, said embryonic stem cell being cultured ex vivo,
wherein said embryonic stem cell interacts with at least one molecule in said ECM, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces in vivo differentiation of said embryonic stem cell into a cardiomyocyte.
14. The composition of claim 13 , wherein said composition further comprises an exogenously added cytokine.