title: Mobilization of progenitor cells into peripheral blood by gamma-tocotrienol: a promising radiation countermeasure.
abstract: 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 (200mg/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.
authors: Armed Forces Radiobiology Research Institute, USUHS, Bethesda, MD 20889-5603, USA.
authors: Sugata
authors: S
authors: Ray
authors: Shilpa S
authors: SS
authors: Kulkarni
authors: Kushal
authors: K
authors: Chakraborty
authors: Roli
authors: R
authors: Pessu
authors: Martin
authors: M
authors: Hauer-Jensen
authors: K Sree
authors: KS
authors: Kumar
authors: Sanchita P
authors: SP
authors: Ghosh
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001596:Benzylamines; D001773:Blood Cells / Q000187:drug effects* / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D002839:Chromans / Q000008:administration & dosage*; D003114:Colony-Forming Units Assay; D000080027:Cyclams; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000943:Antigens, Differentiation; D001596:Benzylamines; D002839:Chromans; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011837:Radiation-Protective Agents; D042461:Vascular Endothelial Growth Factor A; D014810:Vitamin E; D016179:Granulocyte Colony-Stimulating Factor; C013649:plastochromanol 8; C088327:plerixafor