Prostaglandin E2 Increases Hematopoietic Stem Cell Survival and Accelerates Hematopoietic Recovery After Radiation Injury§

Authors

  • Rebecca L. Porter,

    1. Department of Medicine, University of Rochester School of Medicine, Rochester NY
    2. Endocrine Division, University of Rochester School of Medicine, Rochester NY
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  • Mary A. Georger,

    1. Department of Medicine, University of Rochester School of Medicine, Rochester NY
    2. Endocrine Division, University of Rochester School of Medicine, Rochester NY
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  • Olga Bromberg,

    1. Department of Medicine, University of Rochester School of Medicine, Rochester NY
    2. Endocrine Division, University of Rochester School of Medicine, Rochester NY
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  • Kathleen E. McGrath,

    1. Department of Pediatrics, University of Rochester School of Medicine, Rochester NY
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  • Benjamin J. Frisch,

    1. Department of Medicine, University of Rochester School of Medicine, Rochester NY
    2. Endocrine Division, University of Rochester School of Medicine, Rochester NY
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  • Michael W. Becker,

    1. Department of Medicine, University of Rochester School of Medicine, Rochester NY
    2. Hematology Oncology Division, University of Rochester School of Medicine, Rochester NY
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  • Laura M. Calvi

    Corresponding author
    1. Department of Medicine, University of Rochester School of Medicine, Rochester NY
    2. Endocrine Division, University of Rochester School of Medicine, Rochester NY
    • Endocrine Division, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Avenue Box 693, Rochester 14642, New York, USA
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    • Tel.: (585)-275-5011; Fax (585)-273-1288


  • Author contributions: R.L.P.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; M.G: collection and assembly of data and final approval of manuscript; O.B.: collection and assembly of data, data analysis, and final approval of manuscript; K.E.M. and M.W.B.: data analysis and interpretation and final approval of manuscript; B.J.F: collection of data, and final approval of manuscript; L.M.C.: conception and design, financial support, assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS November 21, 2012.

Abstract

Hematopoietic stem and progenitor cells (HSPCs), which continuously maintain all mature blood cells, are regulated within the marrow microenvironment. We previously reported that pharmacologic treatment of naïve mice with prostaglandin E2 (PGE2) expands HSPCs. However, the cellular mechanisms mediating this expansion remain unknown. Here, we demonstrate that PGE2 treatment in naïve mice inhibits apoptosis of HSPCs without changing their proliferation rate. In a murine model of sublethal total body irradiation (TBI), in which HSPCs are rapidly lost, treatment with a long-acting PGE2 analog (dmPGE2) reversed the apoptotic program initiated by TBI. dmPGE2 treatment in vivo decreased the loss of functional HSPCs following radiation injury, as demonstrated both phenotypically and by their increased reconstitution capacity. The antiapoptotic effect of dmPGE2 on HSPCs did not impair their ability to differentiate in vivo, resulting instead in improved hematopoietic recovery after TBI. dmPGE2 also increased microenvironmental cyclooxygenase-2 expression and expanded the α-smooth muscle actin-expressing subset of marrow macrophages, thus enhancing the bone marrow microenvironmental response to TBI. Therefore, in vivo treatment with PGE2 analogs may be particularly beneficial to HSPCs in the setting of injury by targeting them both directly and also through their niche. The current data provide rationale for in vivo manipulation of the HSPC pool as a strategy to improve recovery after myelosuppression. STEM CELLS2013;31:372–383

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