Synergistic effects of stem cell factor and interleukin 6 or interleukin 11 on the expansion of murine hematopoietic progenitors in liquid suspension culture.
The synergistic effects of stem cell factor (SCF) in combination with other growth factors including interleukin (IL)-6, IL-11, IL-3, GM-CSF, G-CSF, IL-1 alpha and interferon-gamma (IFN-gamma) on the expansion of murine hematopoietic progenitors were studied in a short-term liquid suspension culture system. Bone marrow (BM) cells obtained 2 days after 5-fluorouracil (5-FU) injection were cultured for up to 18 days in serum-containing and serum-free cultures in the presence of combinations of various cytokines. The numbers of nucleated cells, total colony-forming cells (CFC), mixed-colony forming units (CFU-Mix) and high-proliferative potential colony-forming cells (HPP-CFC) before and after liquid suspension cultures were measured in the presence of different combinations of cytokines. Combinations of SCF with IL-11, IL-6 or IL-1 alpha markedly increased the numbers of total CFC, CFU-Mix and HPP-CFC. A combination of SCF and IL-3 also expanded the number of total CFC; however, the fold increase was smaller than those of SCF plus IL-11, IL-6 or IL-1 alpha. Three or four factor combinations including SCF with IL-3, IL-6 and IL-11 did not yield increased numbers of total CFC over that supported by SCF plus either IL-6 or IL-11. The addition of IFN-gamma to the culture containing SCF plus IL-11 resulted in a decrease of the expansion efficiency. However, this difference is not statistically significant. In contrast, the addition of IFN-gamma to the cultures containing SCF plus IL-6 did not affect the expansion efficiency. Interestingly, the addition of IL-1 alpha in the culture containing SCF plus IL-3 significantly increased the number of HPP-CFC over that supported by SCF plus IL-3 (p < 0.01). In contrast, IL-1 alpha did not significantly affect the expansion efficiency in the presence of SCF plus IL-6 or IL-11. These results suggest that combinations of SCF plus either IL-6 or IL-11 or a combination of SCF, IL-3 and IL-1 alpha can most effectively expand murine hematopoietic progenitors derived from day-2 post-5-FU BM cells in vitro.
Ariyama
Y
Y
Department of Hygiene, Kyoto Prefectural University of Medicine, Japan.
Misawa
S
S
Sonoda
Y
Y
D000818:Animals; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003470:Culture Media; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000008:administration & dosage; D007375:Interleukin-1 / Q000008:administration & dosage; D017370:Interleukin-11 / Q000008:administration & dosage*; D007377:Interleukin-3 / Q000008:administration & dosage; D015850:Interleukin-6 / Q000008:administration & dosage*; D051379:Mice; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D019089:Stem Cell Factor / Q000008:administration & dosage*; D013997:Time Factors
D003470:Culture Media; D007375:Interleukin-1; D017370:Interleukin-11; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D007371:Interferon-gamma; D019009:Proto-Oncogene Proteins c-kit; D005472:Fluorouracil