Progenitor Cell Mobilization by Gamma-tocotrienol: A Promising Radiation Countermeasure

This article reviews studies of progenitor mobilization with gamma-tocotrienol (GT3), a tocol under advanced development as a radiation countermeasure for acute radiation syndrome (ARS). GT3 protects mice against high doses of ionizing radiation and induces high levels of granulocyte colony-stimulating factor (G-CSF). GT3-induced G-CSF in conjunction with AMD3100 (a chemokine receptor antagonist clinically used to improve the yield of mobilized progenitors) mobilizes progenitors; these mobilized progenitors mitigate injury when infused to mice exposed to acute, high-dose ionizing radiation. The administration of a G-CSF antibody to GT3-injected donor mice abrogated the radiomitigative efficacy of blood or peripheral blood mononuclear cells (PBMC) in irradiated recipient mice. The efficacy of GT3-injected donor mice blood or PBMC was comparable to a recently published article involving blood or mononuclear cells obtained from mice injected with G-CSF. The injected progenitors were found to localize in various tissues of irradiated hosts. The authors demonstrate the efficacy of a bridging therapy in a preclinical animal model that allows the lymphohematopoietic system of severely immunocompromised mice to recover. This suggests that GT3 is a highly effective agent for radioprotection and mobilizing progenitors with significant therapeutic potential. Therefore, GT3 may be considered for further translational development and ultimately for use in humans.