Compositions for Regenerating Defective or Absent Myocardium
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 . A graft for myocardial tissue regeneration, comprising:
acellular extracellular matrix (ECM) from a mammalian tissue source comprising small intestine 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
2 . A graft for myocardial tissue regeneration, 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
3 . A graft for myocardial tissue regeneration, comprising:
acellular extracellular matrix (ECM) from a mammalian tissue source comprising urinary bladder membrane, 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
4 . A graft for myocardial tissue regeneration, comprising:
acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
5 . A graft for myocardial tissue regeneration, comprising:
acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement membrane, 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
6 . A graft for myocardial tissue regeneration, comprising:
acellular extracellular matrix (ECM) from a mammalian tissue source comprising stomach 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
7 . A graft for myocardial tissue regeneration, comprising:
acellular heart extracellular matrix (ECM), 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.
8 . A graft for myocardial tissue regeneration, comprising:
acellular placental extracellular matrix (ECM), 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), 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, when said graft is administered to damaged cardiovascular tissue, said graft induces stem cell proliferation and differentiation of stem cells into cardiomyocytes, and wherein said FGF-2 interacts with said proteoglycans to control and enhance matrix formation and remodeling.