Methods for promoting HSC engraftment
The present invention provides for compositions and methods for modulating hematopoetic stem cell populations by using HCS modulators, which are agents that either increase HSC numbers or decrease HSC numbers as desired by a particular indication. For example, HSC modulators found to increase HSC numbers include prostaglandin E 2 (PGE2) and agents that stimulate the PGE2 pathway. Conversely, HSC modulators that prevent PGE2 synthesis decrease HSC numbers. HCS modulators may be used in vitro, in vivo, or ex vivo.
1. A method for promoting hematopoietic stem cell (HSC) engraftment in a human subject in need thereof, comprising
contacting a population of human HSCs ex vivo with an effective amount of 16,16-dimethyl-PGE 2 to promote engraftment of the HSC in the subject; and
administering the contacted HSCs to the subject, wherein the population of human HSCs is autologous or allogeneic to the subject.
2. The method of claim 1 , wherein the population of human HSCs is obtained from peripheral blood, cord blood, bone marrow, amniotic fluid, or placental blood.
3. The method of claim 1 , wherein the population of human HSCs is obtained from peripheral blood or cord blood.
4. The method of claim 1 , wherein the subject is a candidate for bone marrow or stem cell transplantation, or a subject that has received bone marrow ablating chemotherapy or irradiation therapy.
5. The method of claim 1 , wherein the subject has a solid tumor, myeloma, or lymphoma.
6. The method of claim 1 , wherein the subject has anemia.
7. The method of claim 6 , wherein the anemia is sickle cell anemia, thalassemia, or aplastic anemia.
8. The method of claim 1 , wherein the population of human HSCs is autologous to the subject.
9. The method of claim 1 , wherein the population of human HSCs is allogeneic to the subject.