STEM-CELL FACTOR IMPROVES THE REPOPULATING ABILITY OF PRIMITIVE HEMATOPOIETIC STEM-CELLS AFTER SUBLETHAL IRRADIATION (AND, TO A LESSER EXTENT) AFTER BONE-MARROW TRANSPLANTATION IN MICE

Bone marrow transplantation (BMT) and sublethal irradiation (XRT) caus e profound long-term damage to hematopoietic stem cells, We used the c ompetitive repopulation assay in mice to test the ability of granulocy te-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF), cytokines given in clinical settings to enhance marrow recovery after XRT or BMT and to protect the marrow repopulating ability of pr imitive hematopoietic stem cells (PHSC) after these modalities. The re populating ability of exhaustible? multilineage progenitors (EMP) was also tested after these modalities, with or without cytokines, Repopul ating abilities of EMP and PHSC were significantly reduced after XRT o r BMT; PHSC were preferentially affected, Administration of SCF to C57 B6/J mice after XRT resulted iaa improved EMP and PHSC repopulating ab ility, although progenitor numbers-repopulating units-were not complet ely returned to control levels, Whether given as a single dose car mul tiple doses, GM after XRT did protect PHSC function from the deleterio us effects of XRT, but this was not a significant effect, SCF caused a n increase in PHSC repopulating ability after BMT, but this too was no t a significant difference, GM after BMT had little effect, SCF admini stration before XRT led to severe impairment of PHSC function with ver y little or no stem cell activity observed, Therefore, timing of its a dministration is an important consideration since preadministration of the cytokine before XRT can be extremely harmful to PHSC function.