Expansion of hematopoietic stem cells
Described herein are methods, compositions and kits related to manipulating hematopoietic stem cells and more particularly to methods, compositions and kits related to increasing the number of hematopoietic stem cells in vitro and in vivo. Also described are methods, compositions and kits related to making an expanded population of hematopoietic stem cells (HSCs) and methods, compositions and kits related to using the expanded population of HSCs.
1. A method for selectively increasing the number of short-term hematopoietic stem cells (ST-HSC) in a mammalian subject comprising administering more than one dose of a prostaglandin EP-2 receptor agonist to the mammalian subject, to selectively increase the number of ST-HSCs in the subject, wherein the subject is a donor or a recipient of bone marrow transplant, and wherein the prostaglandin EP-2 receptor agonist is administered to the mammalian subject daily for several days.
2. The method of claim 1 , wherein the subject is a human.
3. The method of claim 1 , wherein the subject has a decreased blood cell level or is at risk for developing a decreased blood cell level as compared to a control blood cell level.
4. The method of claim 1 , wherein the subject has anemia or blood loss.
5. The method of claim 1 , wherein the subject is a bone marrow donor.
6. The method of claim 1 , wherein the subject has depleted bone marrow.
7. The method of claim 1 , wherein the prostaglandin EP receptor agonist is prostaglandin E2 (PGE2) or a derivative thereof.
8. The method of claim 7 , wherein the prostaglandin EP receptor agonist is PGE2.
9. The method of claim 1 , wherein the prostaglandin EP receptor agonist is PGE2.
10. The method of claim 1 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after chemotherapy.
11. The method of claim 1 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after radiation therapy.
12. The method of claim 1 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after bone marrow harvest.
13. The method of claim 1 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after bone marrow transplant.
14. The method of claim 1 , wherein the prostaglandin EP-2 receptor agonist is administered one or more times daily for at least 5, 6, 7, or 8 days.
15. The method of claim 1 , wherein the prostaglandin EP-2 receptor agonist is administered twice daily for at least 5, 6, 7, or 8 days.
16. The method of claim 1 , wherein said prostaglandin EP-2 receptor agonist is administered to the subject before, at the same time, or after chemotherapy, radiation therapy, bone marrow harvest or a bone marrow transplant.
17. A method for selectively expanding a population of short-term hematopoietic stem cells (ST-HSCs) in a mammalian subject in vivo, comprising administering more than one dose of a prostaglandin EP-2 receptor agonist to an unexpanded population of hematopoietic stem cells (HSCs) or a mixture of HSCs and HSC supporting cells in the mammalian subject under conditions that allow the unexpanded population of HSCs to increase in number to form an expanded population of ST-HSCs, wherein the subject is a donor or a recipient of bone marrow transplant, and wherein the prostaglandin EP-2 receptor agonist is administered to the mammalian subject daily for several days.
18. The method of claim 17 , wherein the prostaglandin EP receptor agonist is prostaglandin E2 or a derivative thereof.
19. The method of claim 17 , wherein the prostaglandin EP receptor agonist is PGE2.
20. The method of claim 17 , wherein the ST-HSCs are human ST-HSCs.
21. The method of claim 17 , wherein the subject is a human.
22. The method of claim 17 , wherein the subject has a decreased blood cell level or is at risk for developing a decreased blood cell level as compared to a control blood cell level.
23. The method of claim 17 , wherein the subject has anemia or blood loss.
24. The method of claim 17 , wherein the subject has depleted bone marrow.
25. The method of claim 17 , wherein the prostaglandin EP receptor agonist is prostaglandin E2 or a derivative thereof.
26. The method of claim 17 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after chemotherapy.
27. The method of claim 17 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after radiation therapy.
28. The method of claim 17 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after bone marrow harvest.
29. The method of claim 17 , wherein at least one dose of the prostaglandin EP-2 receptor agonist is administered to the mammalian subject before, at the same time, or after bone marrow transplant.
30. The method of claim 17 , wherein the prostaglandin EP-2 receptor agonist is administered one or more times daily for at least 5, 6, 7, or 8 days.
31. The method of claim 17 , wherein the prostaglandin EP-2 receptor agonist is administered twice daily for at least 5, 6, 7, or 8 days.
32. The method of claim 17 , wherein said prostaglandin EP-2 receptor agonist is administered to the subject before, at the same time, or after chemotherapy, radiation therapy, bone marrow harvest or a bone marrow transplant.
33. A method for selectively increasing the number of short-term hematopoietic stem cells (ST-HSC) in a mammalian subject comprising administering to said subject ONO-8815Ly or ONO-AE1-259 to selectively increase the number of ST-HSCs in said subject.
34. The method of claim 33 comprising administering to said subject ONO-8815Ly.
35. The method of claim 33 comprising administering to said subject ONO-AE1-259.