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Tissue-Specific Stem Cells
Article first published online: 12 FEB 2013
Copyright © 2012 AlphaMed Press
Volume 31, Issue 2, pages 372–383, February 2013
How to Cite
Porter, R. L., Georger, M. A., Bromberg, O., McGrath, K. E., Frisch, B. J., Becker, M. W. and Calvi, L. M. (2013), Prostaglandin E2 Increases Hematopoietic Stem Cell Survival and Accelerates Hematopoietic Recovery After Radiation Injury. STEM CELLS, 31: 372–383. doi: 10.1002/stem.1286
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.
- Issue published online: 12 FEB 2013
- Article first published online: 12 FEB 2013
- Accepted manuscript online: 21 NOV 2012 12:33AM EST
- Manuscript Accepted: 28 OCT 2012
- Manuscript Received: 21 JUN 2012
- National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases. Grant Number: R01 DK 076876
- New York State Stem Cell Initiative
- NYSTEM Investigator Initiated. Grant Number: #N08G-322
- Medical Scientist Training Program. Grant Number: NIH T32 GM-07356
- Hematopoietic stem cells;
- Bone marrow;
- Prostaglandin E2
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