Pulse exposure of haematopoietic grafts to prostaglandin E2in vitro facilitates engraftment and recovery

L. M. Pelus, J. Hoggatt, P. Singh

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Objectives: The aim of this study was to evaluate the effects of prostaglandin E2 (PGE2) on haematopoietic stem cell (HSC) function and determine its mechanism of action. Materials and methods: HSC were exposed to PGE2 for 2h and effects on their homing, engraftment and self-renewal evaluated in vivo. Effects of PGE2 on HSC cell cycle, CXCR4 expression and migration to SDF-1α were analysed in vitro. Apoptosis was evaluated by examination of survivin expression and active caspase-3 levels. Results: Equivalent haematopoietic reconstitution was demonstrated using 4-fold fewer PGE2-treated cells compared to controls. Multilineage reconstitution was stable on secondary transplantation, indicating that PGE2 affects long-term repopulating HSC (LT-HSC) and that enhanced chimaerism of PGE2-pulsed cells results from their initial treatment. PGE2 increased CXCR4 expression on mouse and human HSC, increased their migration to SDF-1αin vitro and enhanced in vivo marrow homing 2-fold, which was blocked by a CXCR4 receptor antagonist. PGE2 pulse exposure reduced apoptosis of mouse and human HSC, with increase in endogenous caspase inhibitor survivin, and concomitant decrease in active caspase-3. Two-fold more HSC entered the cell cycle and proliferated within 24h after PGE2 pulse exposure. Conclusions: These studies demonstrate that short-term PGE2 exposure enhances HSC function and supports the concept of utility of PGE2 as an ex vivo strategy to improve function of haematopoietic grafts, particularly those where HSC numbers are limited.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalCell Proliferation
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Cell Biology

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