Splenic Primitive Hematopoietic Stem Cell (PHSC) Activity Is Enhanced by Steel Factor Because of PHSC Proliferation

To test whether primitive hematopoietic stem cells (PHSCs) are stlmulated by Steel (SI) factor (c-kit ligand) in vivo, donor mice were studied after three or seven daily injections of SI factor. PHSC activity was measured as long-term erythroid and lymphoid competitive repopulating ability. Cells to be tested (usually marrow or spleen cells from treated donors) were mixed with untreated competitor marrow that pro-duces erythrocytes and lymphocytes that are genetically dis-tinguishable from the donors by differences in hemoglobin (Hb) and glucosephosphate isomerase (GPI) markers. These cell mixtures were injected into lethally irradiated hosts, and after 111 t o 293 days, functional abilities of donor PHSC populations were assessed and expressed as percentages of donor-type Hb and GP1 in the host’s circulating erythro-cytes and lymphocytes, respectively. A striking increase i