title: Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors.
abstract: BACKGROUND
  Peripheral blood stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) from healthy donors are commonly used for allogeneic stem cell transplantation. The effect of G-CSF administration on global serum metabolite profiles has not been investigated before.
  
  
  OBJECTIVE
  This study aims to examine the systemic metabolomic profiles prior to and following administration of G-CSF in healthy adults.
  
  
  METHODS
  Blood samples were collected from 15 healthy stem cell donors prior to and after administration of G-CSF 10 µg/kg/day for 4 days. Using a non-targeted metabolomics approach, metabolite levels in serum were determined using ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry.
  
  
  RESULTS
  Comparison of the metabolite profiles of donors before and after G-CSF treatment revealed 239 metabolites that were significantly altered. The major changes of the metabolite profiles following G-CSF administration included alteration of several fatty acids, including increased levels of several medium and long-chain fatty acids, as well as polyunsaturated fatty acids; while there were lower levels of other lipid metabolites such as phospholipids, lysolipids, sphingolipids. Furthermore, there were significantly lower levels of several amino acids and/or their metabolites, including several amino acids with known immunoregulatory functions (methionine, tryptophan, valine). Lastly, the levels of several nucleotides and nucleotide metabolites (guanosine, adenosine, inosine) were also decreased after G-CSF administration, while methylated products were increased. Some of these altered products/metabolites may potentially have angioregulatory effects whereas others may suggest altered intracellular epigenetic regulation.
  
  
  CONCLUSIONS
  Our results show that G-CSF treatment alters biochemical serum profiles, in particular amino acid, lipid and nucleotide metabolism. Additional studies are needed to further evaluate the relevance of these changes in healthy donors.
authors.affiliation: Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kimberley Joanne
authors.identifier: 0000-0003-3310-8176
authors.initials: KJ
authors.lastname: Hatfield
authors.affiliation: Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Guro Kristin
authors.initials: GK
authors.lastname: Melve
authors.affiliation: Department of Clinical Science, University of Bergen, 5021 Bergen, Norway ; Section for Hematology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
keywords: Allogeneic stem cell transplantation; Biochemical; Granulocyte colony-stimulating factor; Metabolomics; Stem cell donor