Granulocyte colony-stimulating factor (G-CSF) is the standard growth factor for mobilizing hematopoietic progenitor cells in healthy peripheral blood progenitor cell (PBPC) donors. G-CSF is given daily for 5 days to PBPC donors prior collecting PBPC concentrates by apheresis. PBPC donors given G-CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. The magnitude of spleen length increase is highly varialbe among individuals and is not affected by donor gender, race, or age. We are currently investigating the mechanisms of G-CSF mobilization of stem cells into the peripheral blood. Plasma protein profiles are being compared before and after G-CSF administration. Associations between the expression of cell adhesion molecules on mature neutrophils and neutrophil precursors and spleen size change will also be investigated.? ? An agent that mobilizes stem cells by a different mechanism than G-CSF is also being to be used clinical to mobilize stem cells. This agent, AMD3100, mobilizes stem cells within a few hours after it is given by directly disrupting the binding of CXCR4 on stem cells with SDF-1 or CXCL12 on marrow storma. In constract, G-CSF mobilizes stem cells after it has been given for 4 to 5 days by the release of proteolytic enzymes that degrade adhesion molecule and by the down-regulation of expression of adhesion molecules. Prelimenary data suggests that stem cells mobilized by AMD3100 and G-CSF have different properties and functions. We have begun to investigate differences in hematopoietic stem cells mobilized by AMD3100 and G-CSF using different gene expression microarrays and micro RNA expression microarrays.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL002099-09
Application #
7593045
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2007
Total Cost
$41,216
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Jin, Ping; Wang, Ena; Ren, Jiaqiang et al. (2008) Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis. J Transl Med 6:39
Stroncek, David F; Jin, Ping; Wang, Ena et al. (2007) Potency analysis of cellular therapies: the emerging role of molecular assays. J Transl Med 5:24
Ren, Jiaqiang; Jin, Ping; Wang, Ena et al. (2007) Pancreatic islet cell therapy for type I diabetes: understanding the effects of glucose stimulation on islets in order to produce better islets for transplantation. J Transl Med 5:1
Stroncek, David; Slezak, Stefanie; Khuu, Hanh et al. (2005) Proteomic signature of myeloproliferation and neutrophilia: analysis of serum and plasma from healthy subjects given granulocyte colony-stimulating factor. Exp Hematol 33:1109-17
Stroncek, David; Dittmar, Kristin; Shawker, Thomas et al. (2004) Transient spleen enlargement in peripheral blood progenitor cell donors given G-CSF. J Transl Med 2:25
Stroncek, David; Shawker, Thomas; Follmann, Dean et al. (2003) G-CSF-induced spleen size changes in peripheral blood progenitor cell donors. Transfusion 43:609-13
Stroncek, David F; Matthews, Cynthia L; Follmann, Dean et al. (2002) Kinetics of G-CSF-induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone. Transfusion 42:597-602
Stroncek, D F; Confer, D L; Leitman, S F (2000) Peripheral blood progenitor cells for HPC transplants involving unrelated donors. Transfusion 40:731-41