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Normal Hemopoiesis And Stemcellogy

Gp130-Signaling synergizes with FL and TPO for the long-term expansion of cord blood progenitors

Abstract

We investigated the effect of a new fusion protein of IL-6 and the soluble IL-6R, H-IL-6, on the long-term ex vivo expansion of hematopoietic progenitors derived from AC133+cord blood cells. H-IL-6, which acts on both IL-6Rα-positive and IL-6Rα-negative cells, effectively synergized with FL and TPO with or without SCF for the propagation of primitive progenitors. However, IL-6 showed a greater synergistic effect with FL and TPO than H-IL-6 for long-term progenitor propagation. During the first 6 weeks of culture under stroma-free serum-containing conditions, IL-6 induced a 1.96 ± 0.64-fold higher expansion of nucleated cells, a 2.28 ± 0.33-fold higher expansion of CD34+ cells and a 2.74 ± 0.28-fold higher expansion of CD34+ AC133+ cells than H-IL-6 in combination with FL and TPO. The propagation of week 6 CAFC was up to four-fold higher in the presence of IL-6 than with H-IL-6. While the expansion of CD34+ and CD34+ AC133+ cells dropped after 5–7 weeks in the stroma-free cultures with FL, TPO and H-IL-6, a sustained expansion for 12 weeks was obtained in the presence of FL, TPO and IL-6. Stroma-contact greatly enhanced the progenitor expansion induced by FL and TPO or FL, TPO and H-IL-6 although the highest proliferation was again obtained in the presence of IL-6. In contrast, the presence of SCF resulted in increased differentiation. Since the majority of primitive progenitors are proposed to be IL-6Rα-negative, the results suggest that the synergistic effect of IL-6 is mediated by accessory cells, which have been more effectively stimulated by IL-6 than by the fusion peptide, H-IL-6, in this culture system.

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Rappold, I., Watt, S., Kusadasi, N. et al. Gp130-Signaling synergizes with FL and TPO for the long-term expansion of cord blood progenitors. Leukemia 13, 2036–2048 (1999). https://doi.org/10.1038/sj.leu.2401597

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  • DOI: https://doi.org/10.1038/sj.leu.2401597

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