Compositions and methods for engraftment and increasing survival of adult muscle stem cells
Embodiments herein relate to compositions and methods for engraftment of and increasing survival of muscle cells in a subject in need thereof. In certain embodiments, compositions including myofibers and/or satellite stem cells may be administered to a subject. Other embodiments relate to compositions and methods for introducing one or more compounds to a subject using cell compositions disclosed herein. Still other embodiments relate to uses of these compositions in kits for portable applications and methods.
1. A composition consisting essentially of:
an enriched population of satellite stem cells characterized by expressing at least
Syndecan-4, ABCG2 and Sca1, whereby the satellite stem cells are capable of generating satellite cells; and
modified fibroblast growth factor (FGF), wherein the modification increases cellular entry of the fibroblast growth factor.
2. The composition of claim 1 , wherein the satellite stem cells are present in an amount of 250 cells or more.
3. The composition of claim 1 , wherein the modified FGF comprises FGF-penetratin.
4. The composition of claim 1 , wherein the modified FGF is full-length FGF, a biologically active fragment thereof, a chimeric protein, fusion protein or a combination thereof.
5. The composition of claim 4 , wherein the modified FGF is a chimeric fibroblast growth factor (FGF) protein comprising: (a) fibroblast growth factor biological activity in the absence of heparan sulfate; and, (b) an ability to enter a living cell in the absence of a receptor that binds to FGF.
6. The composition of claim 1 , wherein the satellite stem cells are obtained by harvesting the cells front one or more human donors.
7. The composition of claim 1 , wherein the satellite stem cells are Pax7 positive.
8. The composition of claim 1 , further comprising a media.
9. The composition of claim 8 , wherein the composition is incubated in media for 12 hours or less.
10. The composition of claim 8 , wherein the media comprises from about 2% serum to about 15% serum.
11. The composition of claim 8 , wherein the satellite stem cells are exposed to the media and the time of exposure is for 24 hours or less.
12. The composition of claim 1 , further comprising a pharmaceutically acceptable excipient.
13. The composition of claim 1 , wherein the enriched population of satellite stem cells are quiescent prior to adding the modified FGF.
14. A kit comprising:
at least one container; and
the composition according to claim 1 .
15. The kit of claim 14 , further comprising at least one additional growth factor.
16. A method for providing one or more of supplement and replenishment for a muscle cell population in a subject in need thereof, comprising:
obtaining an enriched population of satellite stem cells characterized by expressing at least Syndecan-4, ABCG2 and Sca1, whereby the satellite stem cells are capable of generating satellite cells;
incubating the enriched population of satellite stem cells with a media for 24 hours or less;
providing modified fibroblast growth factor (FGF) to the population, wherein the modification increases cellular entry of the FGF; and
administering the enriched population of satellite stem cells to muscle tissue of the subject.
17. The method of claim 16 , wherein the satellite stem cells are from a donor.
18. The method of claim 17 , wherein the donor is an allogeneic donor.
19. The method of claim 17 , wherein the donor is a xenogeneic donor.
20. The method of claim 16 , further comprising injuring myofibers at a site of muscle transplant in the subject or selecting a site of muscle transplant in a subject that is injured and/or undergoing regeneration.
21. The method of claim 20 , wherein injuring the muscle tissue comprises exposing the muscle tissue to a BaCl 2 composition.
22. The method of claim 16 , wherein the subject has one or more of a muscle injury, aging muscle tissue, a muscle disorder or a neurological disorder that causes muscle loss.
23. The method of claim 16 , wherein no more than 30 of the satellite stem cells are administered to the subject.
24. The method of claim 16 , wherein the satellite stem cells are from the subject.
25. The method of claim 16 , wherein incubating the population with a. media comprises incubating the population for 6 hours or less.
26. The method of claim 16 , wherein the modified FGF is full-length FGF, a biologically active fragment thereof, a chimeric protein, fusion protein or a combination thereof.
27. The method of claim 16 , wherein the satellite stem cells are Pax7 positive.
28. The method of claim 16 , wherein the subject is a human.
29. The method of claim 16 , wherein administering comprises one or more of administering by intravenous injection, intra-arterial injection, subcutaneous injection, intramuscular injection or combinations thereof.