Newly emerging roles for prostaglandin E2 regulation of hematopoiesis and hematopoietic stem cell engraftment.
OBJECTIVE
Hematopoietic stem cell (HSC) transplantation is an effective treatment for leukemia, lymphoma, blood disorders, and autoimmune diseases. Successful transplantation is dependent upon efficient homing and engraftment of HSCs. Recently, prostaglandin E2 (PGE2) exposure, either in vivo or ex vivo, has been shown to increase engraftment. These results establish PGE2 as a regulator of hematopoietic development.


RESULTS
The underlying mechanisms of PGE2 regulation of HSC development were poorly understood until recently. Ex-vivo exposure of LSK cells to PGE2 results in increased homing efficiency of HSCs to the murine bone marrow compartment. In addition, in-vivo treatment with PGE2 preferentially expands short-term HSCs without affecting long-term HSC number and engraftment in murine bone marrow. PGE2 acts through EP4 receptors to mediate lymphoid precursor development in the zebrafish. An in-vivo interaction between PGE2 and the Wnt signaling pathways controls HSC engraftment.


CONCLUSIONS
PGE2 has a new role in HSC homing and survival, as well as short-term-HSC engraftment. PGE2 is currently being tested in clinical trials as a potential therapy to enhance HSC engraftment following a transplantation procedure.
Durand
Ellen M
EM
Children's Hospital, Boston, Massachusetts, USA.
Zon
Leonard I
LI
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans
D015232:Dinoprostone