Synergistic effects of stem cell factor and interleukin 6 or interleukin 11 on the expansion of murine hematopoietic progenitors in liquid suspension culture

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Abstract
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-1α and interferon-γ (IFN-γ) 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-1α 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-1α. 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-γ 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-γ to the cultures containing SCF plus IL-6 did not affect the expansion efficiency. Interestingly, the addition of IL-1α 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-1α 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-1α can most effectively expand murine hematopoietic progenitors derived from day-2 post-5-FU BM cells in vitro.