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, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising intestine small submucosa, said ECM comprising endogenous proteoglycans, transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added fibroblast growth factor-2 (FGF-2) and cytokine, said FGF-2 comprising greater than 0.1% by weight of said composition, said FGF-2 being linked to a molecule in said ECM, wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
2. An injectable composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising urinary bladder submucosa, said ECM comprising endogenous proteoglycans, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added fibroblast growth factor-2 (FGF-2) and cytokine, said FGF-2 comprising greater than 0.1 wt. % of said composition, said FGF-2 being linked to said ECM, wherein said FGF-2 saturates available fibroblast cell receptors from the ECM to cells and interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
3. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising stomach submucosa, said ECM comprising native proteoglycans, transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added bioactive component comprising a fibroblast growth factor-2 (FGF-2), said FGF-2 comprising greater than 0.1% by weight of said composition, said FGF-2 being linked to a molecule in said ECM, wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
4. The composition of claim 3 , wherein said composition further comprises an exogenously added cytokine.
5. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement submucosa, said ECM comprising native proteoglycans, transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added bioactive component comprising a fibroblast growth factor-2 (FGF-2), said FGF-2 comprising greater than 0.1% by weight of said composition, said FGF-2 being linked to a molecule in said ECM, wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
6. The composition of claim 5 , wherein said composition further comprises an exogenously added cytokine.
7. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement membrane, said ECM comprising native proteoglycans, transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added bioactive component comprising a fibroblast growth factor-2 (FGF-2), said FGF-2 comprising greater than 0.1% by weight of said composition, said FGF-2 being linked to a molecule in said ECM, wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
8. The composition of claim 7 , wherein said composition further comprises an exogenously added cytokine.
9. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular placental extracellular matrix (ECM), said ECM comprising native proteoglycans, transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added bioactive component comprising a fibroblast growth factor-2 (FGF-2), said FGF-2 comprising greater than 0.1% by weight of said composition, said FGF-2 being linked to a molecule in said ECM, wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
10. The composition of claim 9 ; wherein said composition farther comprises an exogenously added cytokine.
11. An injectable graft composition for myocardial tissue regeneration, said composition comprising acellular heart extracellular matrix (ECM), said ECM comprising native proteoglycans, transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added bioactive component comprising a fibroblast growth factor-2 (FGF-2), said FGF-2 comprising greater than 0.1% by weight of said composition, said FGF-2 being linked to a molecule in said ECM, wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling, wherein, when said composition is administered to damaged cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
12. The composition of claim 11 , wherein said composition further comprises an exogenously added cytokine.