NDLI: Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation

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Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation

Content Provider	Scilit
Author	Hoggatt, Jonathan Singh, Pratibha Sampath, Janardhan Pelus, Louis M.
Copyright Year	2009
Description	Adult hematopoietic stem cells (HSCs) are routinely used to reconstitute hematopoiesis after myeloablation; however, transplantation efficacy and multilineage reconstitution can be limited by inadequate HSC number, or poor homing, engraftment, or self-renewal. Here we report that mouse and human HSCs express prostaglandin E2 (PGE2) receptors, and that short-term ex vivo exposure of HSCs to PGE2 enhances their homing, survival, and proliferation, resulting in increased long-term repopulating cell (LTRC) and competitive repopulating unit (CRU) frequency. HSCs pulsed with PGE2 are more competitive, as determined by head-to-head comparison in a competitive transplantation model. Enhanced HSC frequency and competitive advantage is stable and maintained upon serial transplantation, with full multilineage reconstitution. PGE2 increases HSC CXCR4 mRNA and surface expression, enhances their migration to SDF-1 in vitro and homing to bone marrow in vivo, and stimulates HSC entry into and progression through cell cycle. In addition, PGE2 enhances HSC survival, associated with an increase in Survivin mRNA and protein expression and reduction in intracellular active caspase-3. Our results define novel mechanisms of action whereby PGE2 enhances HSC function and supports a strategy to use PGE2 to facilitate hematopoietic transplantation.
Related Links	http://www.bloodjournal.org/content/113/22/5444.full.pdf
Ending Page	5455
Page Count	12
Starting Page	5444
DOI	10.1182/blood-2009-01-201335
Journal	Blood
Issue Number	22
Volume Number	113
Language	English
Publisher	American Society of Hematology
Publisher Date	2009-05-28
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Cell Proliferation Apoptosis Journal: Blood (Vol- 135, Issue- 22)
Content Type	Text
Resource Type	Article

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