The Phenomenology and Possible Mechanisms of a New Experimental Method for Accelerating Postirradiation Restoration of Hemopoietic Stem Cell Potential

Abstract

Extraction of bone marrow from one or several bones immediately after irradiation, with or without subsequent incubation for a short period under suitable conditions, and subsequent reimplantation into the same organism can reduce the lethal effect of irradiation in a number of species. Extraction plus a period of incubation is referred to as the reimplantation method. The effectiveness is roughly relative to the amount of bone marrow extracted and transplanted. This effect has been demonstrated by assays of 30-45-day survival and of hemopoietic stem cell potential. The effectiveness of the reimplantation method has been tested in a dose range of 6.5 to 8.5 Gy and was found to be 1.2-1.06 in terms of dose reduction factors assayed by bone marrow row cellularity 9 days after exposure and 1.18-1.09 for survival of bone marrow colony-forming units. The favorable effect of incubating irradiated bone marrow with cycloheximide on the stem cell potential has been proven by experiments using a donor-recipient method. The positive effect of the reimplantation procedure and the partial extraction procedure on the stem cell potential in irradiated mice can be shown as soon as 2 h after exposure and the procedures. The results suggest that ther exist some reserves that can be stimulated to accelerate hemopoietic restoration in a heavily irradiated organism. The recruitment of these reserves seems to be related to the response of the structures producing cytokines after lethal irradiation. In addition, repair processes may be involved in the rescue of lethally irradiated hemopoietic stem cells.