SYNCHRONIZED CELL-CYCLE INDUCTION OF ENGRAFTING LONG-TERM REPOPULATING STEM-CELLS

We have recently defined the window for marrow stem cell homing into n onablated hosts as the first 24 hours post-transplant. Within this hom ing window, donor cells rapidly cleared from the peripheral blood and lungs and plateaued in the marrow. We have now assessed the cell-cycle status of the engrafting cells capable of contributing to long-term h ematopoiesis using administration of hydroxyurea (HU), a chemotherapy agent with S-phase cell-cycle specificity. HU was given at very short periods following a male bone marrow transplant (0, 3, 6, 12, and 15 h ours) into female nonablated hosts, and donor cell engraftment was ana lyzed after 6 weeks. The data show that quickly after transplant (12 h ours), greater than half of the engrafting cells capable of contributi ng long-term to all levels of the hematopoietic hierarchy are in S-pha se. Analysis after 6 weeks included whole bone marrow, peripheral bloo d, primitive cells with high proliferative potential, and mature linea ge-restricted marrow cells. These donor cells appear to be naturally s ynchronized. When HU was administered at any of the other time points, there was little evidence of cell death 6 weeks postengraftment. (C) 1997 by The American Society of Hematology.