Enhancement of skeletal muscle stem cell engraftment by dual delivery of VEGF and IGF-1

Patent metadata

Field	Value
Publication number	US-9610328-B2
Application number	US-201113582900-A
Country	US
Kind code	B2
Filing date	Mar 7, 2011
Priority date	Mar 5, 2010
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Mooney David J
• Borselli Cristina
• Vandenburgh Herman
• Shvartsman Dimitry
• Storrie Hannah
• Lichtman Jeff
• Harvard College

Inventors

• Mooney David J
• Borselli Cristina
• Vandenburgh Herman
• Shvartsman Dimitry
• Storrie Hannah
• Lichtman Jeff

Classifications

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title

• A61L2300/414

  Growth factors · CPC title

• A61K35/34

  Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44) · CPC title

• A61L2400/06

  Flowable or injectable implant compositions · CPC title