Newly emerging roles for prostaglandin E2 regulation of hematopoiesis and hematopoietic stem cell engraftment

Purpose of review 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 E-2 (PGE(2)) exposure, either in vivo or ex vivo, has been shown to increase engraftment. These results establish PGE(2) as a regulator of hematopoietic development. Recent findings The underlying mechanisms of PGE(2) regulation of HSC development were poorly understood until recently. Ex-vivo exposure of LSK cells to PGE(2) results in increased homing efficiency of HSCs to the murine bone marrow compartment. In addition, in-vivo treatment with PGE(2) preferentially expands short-term HSCs without affecting long-term HSC number and engraftment in murine bone marrow. PGE(2) acts through EP4 receptors to mediate lymphoid precursor development in the zebrafish. An in-vivo interaction between PGE(2) and the Wnt signaling pathways controls HSC engraftment. Summary PGE(2) has a new role in HSC homing and survival, as well as short-term-HSC engraftment. PGE(2) is currently being tested in clinical trials as a potential therapy to enhance HSC engraftment following a transplantation procedure.