Molecular composition for enhancing and rejuvenating maintenance and repair of mammalian tissues
Methods, pharmaceutical compositions, and kits are provided for treating a subject with an effective amount of an oxytocin receptor (OXTR) agonist and an effective amount of an ALK5 antagonist. In certain aspects, the OXTR agonist may be oxytocin or an oxytocin analog (e.g., a small molecule). The ALK 5 antagonist may be a small molecule, such as 2-(3-(6-Methyl-pyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine, LY2157299, A 83-01, D 4476, GW 788388, LY 364947, Rep Sox, SB 431542, SB 505124, SB 525334, or SD 208. In certain aspects, the amounts of the OXTR agonist and ALK5 antagonist may be sufficient to induce muscle regeneration and/or neural cell regeneration in the subject.
1. A method of enhancing proliferation of a somatic cell, the method comprising:
contacting a somatic cell with oxytocin receptor (OXTR) agonist and ALK5 antagonist,
wherein the contacting is with an amount of the OXTR agonist and ALK5 antagonist effective to enhance proliferation of the somatic cell.
2. The method of claim 1 , wherein the somatic cell is a muscle cell.
3. The method of claim 2 , wherein the muscle cell is a skeletal muscle cell.
4. The method of claim 3 , wherein the skeletal muscle cell is a myoblast.
5. The method of claim 1 , wherein the somatic cell is an activated satellite cell.
6. The method of claim 1 , wherein the somatic cell is a neural cell.
7. The method of claim 6 , wherein the neural cell is a neural stem cell.
8. The method of claim 6 , wherein the neural cell is a neural progenitor cells.
9. The method of claim 1 , wherein the somatic cell is an adult human stem or an adult human progenitor cell.
10. The method of claim 1 , wherein the somatic cell is cell of an aged subject.
11. The method of claim 1 , wherein the somatic cell is an injured cell.
12. The method of claim 11 , wherein the injury is caused by a disease.
13. The method of claim 1 , wherein the somatic cell is a diseased cell.
14. The method of claim 1 , wherein the amount of the OXTR agonist is in the range of 7.5 nM-30 nM.
15. The method of claim 1 , wherein the amount of the ALK5 antagonist is in the range of 0.05 μM-3 μM.
16. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:50.
17. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 50:1.
18. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:40.
19. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:40.
20. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 40:1.
21. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:25.
22. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 25:1.
23. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:10.
24. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 10:1.
25. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:5.
26. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 5:1.
27. The method of claim 1 , wherein the ratio of the OXTR agonist to the ALK5 antagonist is 1:1.
28. The method of claim 1 , wherein the OXTR agonist is oxytocin.
29. The method of claim 1 , wherein the ALK5 antagonist is 2-(3-(6-Methylpyridin-2-yl)-1H-pyrazol-4-yl)-1,5-naphthyridine.
30. The method of claim 1 , wherein the proliferation of the somatic cell is reduced as compared to the proliferation of the same type of somatic cell from a young subject.
31. The method of claim 1 , wherein the proliferation of the somatic cell is reduced as compared to the proliferation of the same type of somatic cell from a healthy adult subject.
32. The method of claim 1 , further comprising assessing proliferation of the somatic cell following the contacting and adjusting the amount of the OXTR agonist and/or the ALK5 antagonist.
33. The method of claim 1 , further comprising assessing proliferation of the somatic cell following the contacting and increasing the amount of the OXTR agonist.
34. The method of claim 1 , further comprising assessing proliferation of the somatic cell following the contacting and decreasing the amount of the OXTR agonist.
35. The method of claim 1 , further comprising assessing proliferation of the somatic cell following the contacting and increasing the amount of the ALK5 antagonist.
36. The method of claim 1 , further comprising assessing proliferation of the somatic cell following the contacting and decreasing the amount of the ALK5 antagonist.
37. The method of claim 1 , further comprising assessing proliferation of the somatic cell following the contacting and repeating the contacting on a schedule.
38. The method of claim 37 , further comprising assessing proliferation of the somatic cell following the repeated contacting and adjusting the contacting schedule.