title: Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34+ cells mobilized by G-CSF and plerixafor.
abstract: OBJECTIVE
  Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34(+) cells in rhesus macaques. We sought to evaluate whether these CD34(+) cells can stably reconstitute blood cells with lentiviral gene marking.
  
  
  METHODS
  We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34(+) cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.
  
  
  RESULTS
  G-CSF and plerixafor mobilization resulted in CD34(+) cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) expression was greater in G-CSF and plerixafor-mobilized CD34(+) cells when compared to G-CSF alone. Animals transplanted with G-CSF and plerixafor-mobilized cells showed engraftment of all lineages, similar to animals who received G-CSF and stem cell factor-mobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and plerixafor-mobilized CD34(+) cells. One animal in the G-CSF and plerixafor group developed cold agglutinin-associated skin rash during the first 3 months of rapid lymphocyte recovery. One year after transplantation, all animals had 2% to 10% transgene expression in all blood cell lineages.
  
  
  CONCLUSIONS
  G-CSF and plerixafor-mobilized CD34(+) cells accelerate lymphocyte engraftment and contain hematopoietic stem cell capable of reconstituting multilineage blood cells. These findings indicate important differences to consider in plerixafor-based hematopoietic stem cell mobilization protocols in rhesus macaques.
authors.affiliation: Molecular and Clinical Hematology Branch, National Heart Lung and Blood Institute/National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Naoya
authors.initials: N
authors.lastname: Uchida
authors.forename: Aylin
authors.initials: A
authors.lastname: Bonifacino
authors.forename: Allen E
authors.initials: AE
authors.lastname: Krouse
authors.forename: Mark E
authors.initials: ME
authors.lastname: Metzger
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Csako
authors.forename: Agnes
authors.initials: A
authors.lastname: Lee-Stroka
authors.forename: Ross M
authors.initials: RM
authors.lastname: Fasano
authors.forename: Susan F
authors.initials: SF
authors.lastname: Leitman
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Mattapallil
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hsieh
authors.forename: John F
authors.initials: JF
authors.lastname: Tisdale
authors.forename: Robert E
authors.initials: RE
authors.lastname: Donahue
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001596:Benzylamines; D000080027:Cyclams; D004357:Drug Synergism; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008253:Macaca mulatta; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D053650:Interleukin-3 Receptor alpha Subunit; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; C088327:plerixafor