SYNERGISTIC EFFECTS OF INTERLEUKIN-11 WITH OTHER GROWTH-FACTORS ON THE EXPANSION OF MURINE HEMATOPOIETIC PROGENITORS AND MAINTENANCE OF STEM-CELLS IN LIQUID CULTURE

The effect of interleukin-11 (IL-11), alone and in combination with ot her hematopoietic growth factors, was studied in liquid suspension cul tures of murine bone marrow. Stem and progenitor cell contents of inpu t bone marrow 2 days after 5-fluorouracil (5-FU) treatment (FU(2d)BM) and lineage-depleted, Sca-1-positive FU(2d)BM (Lid(-)Sca(+)FU(2d)BM) w ere compared with output values obtained after 6 days in different gro wth factor combinations. Stem and progenitor cell recoveries were meas ured by long-term in vivo competitive repopulation, spleen colony-form ing unit (CFU-S), and in vitro limiting dilution long-term bone marrow culture (cobblestone area-forming cell [CAFC]) assays. IL-11, IL-3, I L-6, and Steel factor (SF) were tested separately and in combinations of two, three, and four factors. IL-11 was incapable of maintaining th e survival of stem or progenitor cells as a single agent but synergize d with either IL-3 or SF to expand progenitor cell output in cultures of FU(2d)BM. IL-11 greatly enhanced progenitor cell expansion from FU( 2d)BM when added to two- and three-factor combinations of SF, IL-3, an d IL6, The recovery of long-term repopulating ability was enhanced fou r-fold by incubation in SF plus IL-11 compared to SF alone. IL-11 in c ombination with SF, IL-3, and IL-6 stimulated a 24,000-fold expansion of progenitor cells from stem cell-enriched Lin(-)Sca(+)FU(2d)BM, Over all, the results indicate that IL-11 is a potent synergistic factor fo r stem cell proliferation and expansion of progenitors in liquid cultu re.