Hematopoietic progenitor cell mobilization in mice by sustained delivery of granulocyte colony-stimulating factor

Simon N. Robinson, Jennifer M. Chavez, Joan M. Blonder, Vladimir M. Pisarev, R. Lee Mosley, Hongxun Sang, Gary J. Rosenthal, James E. Talmadge

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The objective of these studies was to determine the effect of sustained delivery of growth factors (GFs) on hematopoietic progenitor cells (HPCs) in mice. In these studies, granulocyte colony-stimulating factor (G-CSF) was administered using the poloxamer-based matrix, ProGelz (PG) and G-CSF, and pharmacokinetics (PKs) and HPC mobilization was assessed. A single injection of G-CSF formulated in PG (17% poloxamer-407 and 5% hydroxypropyl methylcellulose [HPMC]) administered to BALB/c mice mobilized HPC significantly more rapidly to the spleen, but not the blood, than multiple injections of saline-formulated G-CSF. Two days after a single injection of PG G-CSF, the frequency of colony-forming unit-culture (CFU-c) in the spleen was increased 289-fold compared with an 8-fold increase after 2 days of twice-daily injections of saline-formulated G-CSF. Indeed, 4 days of twice-daily G-CSF injections were required to achieve the same level of HPC mobilization. In contrast, a similar mobilization of HPC to the blood was observed between PG and saline-formulated G-CSF. The mechanism for the accelerated and increased mobilization to the spleen by the PG-formulation of G-CSF is due, in part, to its increased bioavailability (>1.5-fold), Tmax (6-fold), and prolonged elimination (Tβ) half-life (>3-fold) as compared with a saline formulation. In addition, we observed a more rapid trafficking of the PG G-CSF to the marrow, which could also facilitate mobilization.

Original languageEnglish (US)
Pages (from-to)490-500
Number of pages11
JournalJournal of Interferon and Cytokine Research
Volume25
Issue number8
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

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