Enhancement of skeletal muscle stem cell engraftment by dual delivery of VEGF and IGF-1
An improved device and method for extended repair and regeneration of muscle tissue. An exemplary device comprises (a) a scaffold comprising an ECM component; (b) a combination of growth factors such as VEGF and IGF; and (c) a population of myogenic cells. Implantation of the device leads to muscle regeneration and repair over an extended period of time.
1. A method of enhancing muscle tissue repair or regeneration,
comprising introducing into a muscle tissue of a human subject an injectable device comprising an alginate hydrogel comprising a combination of vascular endothelial growth factor 165 (VEGF 165 ) and insulin-like growth factor-1 (IGF-1), wherein the alginate hydrogel comprises oxidized alginate, wherein the VEGF 165 and the IGF-1 are released from the device into said muscle tissue, and wherein introduction of said device comprising a combination of VEGF 165 and IGF-1 provides a synergistic muscle tissue regeneration effect in the human subject.
2. The method of claim 1 , wherein said muscle tissue comprises skeletal muscle tissue.
3. The method of claim 1 , wherein said muscle tissue comprises smooth muscle tissue.
4. The method of claim 1 , wherein said muscle tissue comprises cardiac muscle tissue.
5. The method of claim 1 , wherein introduction of said device comprising a combination of VEGF 165 and IGF-1 provides an increase in blood vessel density in said muscle tissue.
6. The method of claim 1 , wherein regional blood perfusion of muscle tissue is increased following introduction of said device.
7. The method of claim 1 , wherein said device is introduced into a muscle tissue of the human subject using a needle.
8. The method of claim 1 , wherein said device comprises macropores.
9. The method of claim 1 , wherein said device further comprises a population of myogenic cells.
10. The method of claim 9 , wherein said myogenic cells comprise myoblasts.
11. The method of claim 9 , wherein said myogenic cells comprise satellite cells.
12. The method of claim 9 , wherein said myogenic cells are seeded into or onto said hydrogel ex vivo.
13. The method of claim 1 , wherein the alginate hydrogel comprises low molecular weight alginate and high molecular weight alginate.
14. The method of claim 13 , wherein the alginate hydrogel comprises oxidized low molecular weight alginate and oxidized high molecular weight alginate.
15. The method of claim 14 , wherein the ratio of low molecular weight to high molecular weight alginate is 1:1.
16. The method of claim 1 , wherein the alginate hydrogel comprises 1%, 5%, or 10% oxidized alginate.
17. A method of treating an ischemic disease or ischemic injury in a human subject comprising introducing into a tissue of the human subject a device comprising an alginate hydrogel comprising a combination of vascular endothelial growth factor 165 (VEGF 165 ) and insulin-like growth factor-1 (IGF 1), wherein the alginate hydrogel comprises oxidized alginate, wherein the VEGF 165 and the IGF-1 are released from the device into the tissue, and wherein introduction of said device comprising a combination of VEGF 165 and IGF-1 provides a synergistic muscle tissue regeneration or revascularization effect in the human subject.
18. The method of claim 17 , wherein the ischemic disease comprises chronic ischemia.
19. The method of claim 1 , wherein the alginate hydrogel further comprises non-oxidized alginate.