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 an acellular extracellular matrix (ECM) from a mammalian tissue source comprising small intestine submucosa, said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β (TGF-β), said TGF-β comprising at least 0.1% by weight of said composition,
said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
2. The composition of claim 1 , wherein said composition further comprises an exogenously added cytokine.
3. An injectable graft composition for myocardial tissue regeneration, said composition comprising an acellular extracellular matrix (ECM) from a mammalian tissue source comprising urinary bladder submucosa, said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β (TGF-β), said TGF-β comprising at least 0.1% by weight of said composition,
said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased 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 an acellular extracellular matrix (ECM) from a mammalian tissue source comprising stomach submucosa, said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β (TGF-β), said TGF-β comprising at least 0.1% by weight of said composition,
said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased 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 an acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement submucosa, said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β(TGF-β), said TGF-β comprising at least 0.1% by weight of said composition, said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased 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 an acellular extracellular matrix (ECM) from a mammalian tissue source comprising liver basement membrane, said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β (TGF-β), said TGF-β comprising at least 0.1% by weight of said composition,
said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
10. The composition of claim 9 , wherein said composition further comprises an exogenously added cytokine.
11. An injectable graft composition for myocardial tissue regeneration, said composition comprising an acellular placental extracellular matrix (ECM), said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β (TGF-β), said TGF-β comprising at least 0.1% by weight of said composition,
said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased 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.
13. An injectable graft composition for myocardial tissue regeneration, said composition comprising an acellular heart extracellular matrix (ECM), said ECM comprising endogenous proteoglycans, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), said ECM further comprising an exogenously added transforming growth factor-β (TGF-β), said TGF-β comprising at least 0.1% by weight of said composition,
said TGF-β being linked to at least one molecule in said ECM, wherein said TGF-β interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said composition is administered to damaged or diseased cardiovascular tissue, said composition induces stem cell proliferation and differentiation of stem cells into cardiomyocytes.
14. The composition of claim 13 , wherein said composition further comprises an exogenously added cytokine.