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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-12

AUTHORS

I Rappold, SM Watt, N Kusadasi, S Rose-John, J Hatzfeld, RE Ploemacher

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-6Ralpha-positive and IL-6Ralpha-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-6Ralpha-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. More... »

PAGES

2036

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2401597

DOI

http://dx.doi.org/10.1038/sj.leu.2401597

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028780727

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10602426


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