HEMATOPOIETIC STEM-CELLS IN THE BLOOD AFTER STEM-CELL FACTOR AND INTERLEUKIN-11 ADMINISTRATION - EVIDENCE FOR DIFFERENT MECHANISMS OF MOBILIZATION

Peripheral blood stem cells and progenitor cells, collected during rec overy from exposure to cytotoxic agents or after cytokine administrati on, are being increasingly used in clinical bone marrow transplantatio n. To determine factors important for mobilization of both primitive s tem cells and progenitor cells to the blood, we studied the blood and splenic and marrow compartments of intact and splenectomized mice afte r administration of recombinant human interleukin-11 (rhIL-11), recomb inant rat stem cell factor (rrSCF), and IL-11 + SCF. IL-11 administrat ion increased the number of spleen colony-forming units (CPU-S) in bot h the spleen and blood, but did not increase blood long-term marrow-re populating ability (LTRA) in intact or splenectomized mice, SCF admini stration increased the number of CFU-S in both the spleen and blood an d did not increase the blood or splenic LTRA of intact mice, but did i ncrease blood LTRA to normal marrow levels in splenectomized mice. The combination of IL-11 + SCF syngeristically enhanced mobilization of l ong-term marrow-repopulating cells from the marrow to the spleen of in tact mice and from the marrow to the blood of splenectomized mice. The se data, combined with those of prior studies showing granulocyte colo ny-stimulating factor mobilization of long-term marrow repopulating ce lls from the marrow to the blood of mice with intact spleens, suggest different cytokine-induced pathways for mobilization of primitive stem cells. (C) 1995 by The American Society of Hematology.