title: Plasma from poorly mobilizing human subjects inhibits cytokine-induced murine blood stem-cell mobilization.
abstract: BACKGROUND
  Cytokine-induced mobilization of hematopoietic stem/progenitor cells to the circulation facilitates efficient harvest of blood stem cells by leukapheresis. Up to 30% of autologous, and 10-20% of allogeneic blood stem-cell donors respond poorly to mobilizing cytokines and preliminary studies implicated a circulating inhibitor of mobilization.
  
  
  METHODS
  In this study, plasma from 11 allogeneic and 23 autologous stem cell donors was assayed for inhibition of mobilization in mice.
  
  
  RESULTS
  There were significant correlations between CD34(+) cells collected/kg human donor weight and spleen weight, CD34(+) CD45(+) cells, GMCFC and HPP-CFC per spleen in murine recipients of these plasma samples. Overall, there was a positive association between transforming growth factor beta (TGF-beta) levels and CD34(+) cells per liter of blood processed (LBP). However, when arbitrarily segregated into good versus poor mobilizers, based on less or greater than 15 million CD34(+) cells collected per LBP, the majority (64%) of normal donors were good mobilizers. The majority of the poor mobilizers (83%) were patients. For a subset of 12 individuals whose plasma strongly inhibited mobilization in the mouse, a significant positive correlation of the extent of inhibition with TGF-beta levels was found. For 11 individuals whose plasma, based on colony assays, enhanced mobilization when injected into mice, no correlation with TGF-beta levels was evident.
  
  
  CONCLUSIONS
  Elevated plasma TGF-beta levels in some stem-cell donors may be associated with poor stem-cell mobilization. It remains to be determined whether elevation of TGF-beta levels is a cause of, or a compensatory response to, poor mobilization.
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-4390, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Sharp
authors.forename: T R
authors.initials: TR
authors.lastname: McGuire
authors.forename: S L
authors.initials: SL
authors.lastname: Mann
authors.forename: B
authors.initials: B
authors.lastname: Murphy
authors.forename: A
authors.initials: A
authors.lastname: Kessinger
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology; D051379:Mice; D010949:Plasma / Q000276:immunology*; D013223:Statistics as Topic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D016212:Transforming Growth Factor beta