STUDIES ON THE HYPERTHERMIC SENSITIVITY OF THE MURINE HEMATOPOIETIC STEM-CELL COMPARTMENT .2. HEAT EFFECT ON DONOR STEM-CELLS WITH LONG-TERM REPOPULATING ABILITY

Variations in hyperthermic sensitivity among different hematopoietic p rogenitor and stem cell populations of the bone marrow have been previ ously described for clonogenic subsets responsible for short-term hema topoiesis. However, less is known of the heat sensitivity of more prim itive stem cells capable of long-term repopulation in irradiated recip ients. In the present study, control and heat-treated (60 minutes at 4 3 degrees C) donor bone marrow cells from congenic B6-Gpi-1(a) mice we re transplanted at different cell doses (10(4), 10(5), 10(6), and 10(7 ) nucleated cells) in pre-irradiated (6 Gy) BG-Gpi-lb mice. The develo pment and levels of donor marrow engraftment were determined from bloo d Gpi phenotyping, and the bone marrow dose required for equivalent lo ngterm engraftment at 20 weeks provided an estimate of the surviving f raction corresponding to primitive stem cells of long-term repopulatin g ability (LTRA). Comparison with previous bone marrow cell survival v alues demonstrates that LTRA cells are less sensitive to hyperthermic treatment than other hematopoietic subsets, confirming a relationship between the heat sensitivity and the hierarchical structure of the hem atopoietic stem cell compartment.