title: Prostaglandin E2 enhances long-term repopulation but does not permanently alter inherent stem cell competitiveness.
abstract: Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for malignant and nonmalignant hematologic diseases and metabolic disorders. Although successful, hematopoietic transplantation can be hindered by inadequate stem cell number or poor engrafting efficiency. To overcome these deficits, we and others have previously reported the HSC-enhancing ability of a short-term exposure of prostaglandin E2 (PGE2); this strategy has now progressed to phase 1 clinical trials in double cord blood transplantation. To further analyze the short- and long-term effects of HSC exposure to PGE2, we followed the repopulation kinetics of PGE2-treated hematopoietic grafts through 5 serial transplantations and compared inherent long-term competitiveness in a HSC head-to-head secondary transplantation model. Treatment with PGE2 did not result in a long-term increase in HSC competitiveness, lineage bias, or enhanced proliferative potential, demonstrating that pulse exposure to PGE2 results in transient increases in HSC homing and engraftment potential.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hoggatt
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Mohammad
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.forename: Louis M
authors.initials: LM
authors.lastname: Pelus
mesh_terms: D000818:Animals; D002452:Cell Count; D019070:Cell Lineage / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D006085:Graft Survival / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015232:Dinoprostone
references.citation: Nat Biotechnol. 2011 Oct 02;29(10):928-33
references.pmid: 21964413
references.citation: Transplantation. 1976 Sep;22(3):287-93
references.pmid: 788254
references.citation: Blood. 2009 Dec 3;114(24):4968-78
references.pmid: 19752395
references.citation: Blood. 2013 Oct 24;122(17):3074-81
references.pmid: 23996087
references.citation: Blood. 2013 Jul 25;122(4):523-32
references.pmid: 23719303
references.citation: Leukemia. 2010 Dec;24(12):1993-2002
references.pmid: 20882043
references.citation: J Clin Invest. 1982 Sep;70(3):568-78
references.pmid: 6286727
references.citation: Nature. 2007 Jun 21;447(7147):1007-11
references.pmid: 17581586
references.citation: Cell. 2009 Mar 20;136(6):1136-47
references.pmid: 19303855
references.citation: Mol Cancer Ther. 2004 Aug;3(8):1031-9
references.pmid: 15299086
references.citation: Curr Opin Hematol. 2013 Jul;20(4):257-64
references.pmid: 23615054
references.citation: Curr Opin Hematol. 2006 Jul;13(4):243-8
references.pmid: 16755220
references.citation: Curr Pharm Des. 2006;12(8):943-54
references.pmid: 16533161
references.citation: Science. 2010 Mar 26;327(5973):1650-3
references.pmid: 20339075
references.citation: Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):3-9
references.pmid: 21722751
references.citation: Blood. 2009 May 28;113(22):5444-55
references.pmid: 19324903
references.citation: Immunol Res. 1989;8(3):176-84
references.pmid: 2664032
references.citation: Exp Hematol. 2009 Sep;37(9):1084-95
references.pmid: 19501128
references.citation: Leuk Res. 1981;5(1):65-71
references.pmid: 7230872