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 other hematopoietic growth factors, was studied in liquid suspension cultures of murine bone marrow. Stem and progenitor cell contents of input bone marrow 2 days after 5-fluorouracil (5-FU) treatment (FU2dBM) and lineage-depleted, Sca-1-positive FU2dBM (Lin-Sca+Fu2dBM) were compared with output values obtained after 6 days in different growth factor combinations. Stem and progenitor cell recoveries were measured by long-term in vivo competitive repopulation, spleen colony-forming unit (CFU-S), and in vitro limiting dilution long-term bone marrow culture (cobblestone area-forming cell [CAFC]) assays. IL-11, IL-3, IL-6, and Steel factor (SF) were tested separately and in combinations of two, three, and four factors. IL-11 was incapable of maintaining the survival of stem or progenitor cells as a single agent but synergized with either IL-3 or SF to expand progenitor cell output in cultures of FU2dBM. IL-11 greatly enhanced progenitor cell expansion from FU2dBM when added to two- and three-factor combinations of SF, IL-3, and IL-6. The recovery of long-term repopulating ability was enhanced four-fold by incubation in SF plus IL-11 compared to SF alone. IL-11 in combination with SF, IL-3, and IL-6 stimulated a 24,000-fold expansion of progenitor cells from stem cell-enriched Lin-Sca+FU2dBM. Overall, the results indicate that IL-11 is a potent synergistic factor for stem cell proliferation and expansion of progenitors in liquid culture.
Neben
S
S
Genetics Institute, Cambridge, MA 02140.
Donaldson
D
D
Sieff
C
C
Mauch
P
P
Bodine
D
D
Ferrara
J
J
Yetz-Aldape
J
J
Turner
K
K
D000818:Animals; D002478:Cells, Cultured; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006133:Growth Substances / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D017370:Interleukin-11 / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D006133:Growth Substances; D017370:Interleukin-11; D005472:Fluorouracil