Preclinical development of a bridging therapy for radiation casualties

Objective: Victims of a terrorist attack presenting with the hematopoietic syndrome resulting from exposure to excessive levels of ionizing radiation will succumb to sepsis if not adequately treated. The probability of survival is increased substantially if the victim's immune system is allowed to recover before sepsis sets in. We report here preclinical development of a new bridging therapy that will allow the victim's immune system to recover from damage caused by ionizing radiation. Materials and Methods: The hematopoietic progenitor cells in blood from tocopherol succinate (TS)-injected mice were analyzed quantitatively by standard in vitro soft matrix colony procedures. CD2F1 mice were irradiated with lethal, whole-body doses (9.2 Gy) of ⁶⁰Co γ-rays and then transfused intravenously (periorbital sinus, venous plexus behind the eye) with whole blood, peripheral blood mononuclear cells, or plasma from TS-injected mice 2 and 24 hours postirradiation. Survival was monitored for 30 days after transfusion of whole blood, peripheral blood mononuclear cells, or plasma. Results: Progenitor cell analyses revealed that hematopoietic progenitors were mobilized into the peripheral blood of TS-injected mice. Our results demonstrated that infusions of whole blood or peripheral blood mononuclear cells from TS-injected mice greatly improved chances of extended survival of lethally irradiated mice. Conclusion: TS-stimulated granulocyte colony-stimulating factor mobilizes high numbers of progenitors into the peripheral circulation; in turn, this blood-these progenitors-can be used upon subsequent transfusion to effectively mitigate and repair primary acute radiation injury. The transfused cells act secondarily as a bridging therapy for irradiated mice while their own immune system recovers from the radiation-induced damage.