TY - JOUR
T1 - Mobilization of progenitor cells into peripheral blood by gamma-tocotrienol
T2 - A promising radiation countermeasure
AU - Ray, Sugata
AU - Kulkarni, Shilpa S.
AU - Chakraborty, Kushal
AU - Pessu, Roli
AU - Hauer-Jensen, Martin
AU - Kumar, K. Sree
AU - Ghosh, Sanchita P.
N1 - Funding Information:
The authors would like to acknowledge Kevin Hieber and Raymond Toles for technical help. This study was supported by U.S. Department of Defense Threat Reduction Agency grant H.10027_07_AR_R, administered by The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
PY - 2013/3
Y1 - 2013/3
N2 - Gamma-tocotrienol (GT3), a vitamin E isoform, is shown to induce high levels of granulocyte colony stimulating factor (G-CSF) in mice. G-CSF is a key cytokine used for stimulation of hematopoiesis, and mobilization of hematopoietic stem and progenitor cells into peripheral blood. GT3 is also shown to induce vascular endothelial growth factor (VEGF), another important cytokine necessary for vasculogenesis and endothelial progenitor mobilization. Since GT3 induces both these cytokines, we tested whether GT3 mobilizes hematopoietic and endothelial progenitors in mice. GT3 (200 mg/kg) was injected in 10-week-old CD2F1 mice and mobilization of progenitors in peripheral blood was analyzed at 24, 48, and 72 h post-administration. Circulating hematopoietic progenitor cells (HPCs, Lin-, cKit+), endothelial progenitor cells (EPCs, Lin-, CD34+, Flk+), and stromal progenitor cells (SPCs, Lin-, CD29+, CD105+) in peripheral blood mononuclear cells (PBMCs) were analyzed simultaneously by flow cytometry. Mobilized HPCs, EPCs and SPCs in PBMC were also measured by colony-forming unit (CFU) assay in progenitor-specific media. Three groups of mice received vehicle, GT3 and GT3 plus AMD3100, a receptor antagonist used to enhance mobilization. GT3 induced significant mobilization of all three progenitor cell types compared to vehicle in peripheral blood; AMD3100 enhanced GT3-induced mobilization even further. Mobilization of progenitor cells in peripheral blood by GT3 indicates that GT3 can be used as an alternative to G-CSF and VGEF to mobilize HPCs and EPCs.
AB - Gamma-tocotrienol (GT3), a vitamin E isoform, is shown to induce high levels of granulocyte colony stimulating factor (G-CSF) in mice. G-CSF is a key cytokine used for stimulation of hematopoiesis, and mobilization of hematopoietic stem and progenitor cells into peripheral blood. GT3 is also shown to induce vascular endothelial growth factor (VEGF), another important cytokine necessary for vasculogenesis and endothelial progenitor mobilization. Since GT3 induces both these cytokines, we tested whether GT3 mobilizes hematopoietic and endothelial progenitors in mice. GT3 (200 mg/kg) was injected in 10-week-old CD2F1 mice and mobilization of progenitors in peripheral blood was analyzed at 24, 48, and 72 h post-administration. Circulating hematopoietic progenitor cells (HPCs, Lin-, cKit+), endothelial progenitor cells (EPCs, Lin-, CD34+, Flk+), and stromal progenitor cells (SPCs, Lin-, CD29+, CD105+) in peripheral blood mononuclear cells (PBMCs) were analyzed simultaneously by flow cytometry. Mobilized HPCs, EPCs and SPCs in PBMC were also measured by colony-forming unit (CFU) assay in progenitor-specific media. Three groups of mice received vehicle, GT3 and GT3 plus AMD3100, a receptor antagonist used to enhance mobilization. GT3 induced significant mobilization of all three progenitor cell types compared to vehicle in peripheral blood; AMD3100 enhanced GT3-induced mobilization even further. Mobilization of progenitor cells in peripheral blood by GT3 indicates that GT3 can be used as an alternative to G-CSF and VGEF to mobilize HPCs and EPCs.
KW - Endothelial
KW - Gamma-tocotrienol
KW - Hematopoietic
KW - Mobilization
KW - Progenitors
KW - Stromal
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UR - http://www.scopus.com/inward/citedby.url?scp=84874601221&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2012.12.034
DO - 10.1016/j.intimp.2012.12.034
M3 - Article
C2 - 23415908
AN - SCOPUS:84874601221
SN - 1567-5769
VL - 15
SP - 557
EP - 564
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 3
ER -