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 extracellular matrix (ECM) from a mammalian tissue source comprising acellular small intestine submucosa, said ECM comprising endogenous proteoglycans, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added vascular endothelial growth factor (VEGF) and cytokine, said VEGF component comprising greater than 0.1% by weight of said composition, said VEGF component being linked to a molecule in said ECM, wherein said VEGF component interacts with said proteoglycans to control matrix formation and remodeling, wherein, when said ECM composition is administered to damaged or diseased cardiovascular tissue, said ECM composition induces stem cell proliferation, differentiation of stem cells into cardiomyocytes and, thereby, angiogenesis.
2. An injectable graft composition 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 fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added vascular endothelial growth factor (VEGF), said VEGF being linked to said ECM, wherein said VEGF interacts with said proteoglycans to control 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. The composition of claim 2 , wherein said composition further comprises an exogenously added cytokine.
4. An injectable graft composition 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 fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added vascular endothelial growth factor (VEGF), said VEGF being linked to said ECM, wherein said VEGF interacts with said proteoglycans to control 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.
5. The composition of claim 4 , wherein said composition further comprises an exogenously added cytokine.
6. An injectable graft composition 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 fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added vascular endothelial growth factor (VEGF), said VEGF being linked to said ECM, wherein said VEGF interacts with said proteoglycans to control 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.
7. The composition of claim 6 , wherein said composition further comprises an exogenously added cytokine.
8. An injectable graft composition for myocardial tissue regeneration, comprising acellular placental extracellular matrix (ECM), said ECM comprising endogenous proteoglycans, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added vascular endothelial growth factor (VEGF), said VEGF being linked to said ECM, wherein said VEGF interacts with said proteoglycans to control 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.
9. The composition of claim 8 , wherein said composition further comprises an exogenously added cytokine.
10. An injectable graft composition for myocardial tissue regeneration, comprising acellular heart extracellular matrix (ECM), said ECM comprising endogenous proteoglycans, transforming growth factor beta (TGF-β) and fibroblast growth factor-2 (FGF-2), said ECM further comprising an exogenously added vascular endothelial growth factor (VEGF) and cytokine, said VEGF being linked to said ECM, wherein said VEGF interacts with said proteoglycans to control 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.