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A bioactive designer cytokine for human hematopoietic progenitor cell expansion

Nature Biotechnology volume 15, pages 142–145 (1997)Cite this article

Abstract

Efficient expansion of hematopoietic progenitor cells requires, at least, the simultaneous stimulation of the receptors c-kit and gp130. While c-kit is activated by SCF; gp130, in cells which do not express sufficient amounts of IL-6R, can be activated by the complex of soluble IL-6R (slL-6R) and IL-6. The therapeutic use of IL-6/sIL-6R, however, has been hampered by the high concentrations of the sIL-6R protein required. We have designed a fusion protein of sIL-6R and IL-6, linked by a flexible peptide chain, that was expressed to high levels. On gp130 expressing cells the fusion protein turned out to be fully active at 100 to 1,000-fold lower concentration than the combination of unlinked IL-6 and IL-6R. The fusion protein was used to effectively expand human hematopoietic progenitor cells ex vivo in a dose dependent fashion.

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Author information

Author notes

  1. Stefan Rose-John: Corresponding author (e-mail: rose@mzdmza.zdv.uni-mainz.de)

Authors and Affiliations

  1. I. Department of Medicine-Section-Pathophysiology, Mainz University, D-55101, Mainz, Germany

    Martina Fischer, Karl-Josef Kallen & Stefan Rose-John

  2. III. Department of Medicine, Mainz University, D-55101, Mainz, Germany

    Jutta Goldschmitt & Christian Peschel

  3. Central Laboratory of the Netherlands, Amsterdam, 1066 CX

    Just P. G. Brakenhoff

  4. Department of Biochemistry, RWTH Aachen, D-52057, Aachen, Germany

    Axel Wollmer & Joachim Grötzinger

Authors
  1. Martina Fischer
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  2. Jutta Goldschmitt
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Fischer, M., Goldschmitt, J., Peschel, C. et al. A bioactive designer cytokine for human hematopoietic progenitor cell expansion. Nat Biotechnol 15, 142–145 (1997). https://doi.org/10.1038/nbt0297-142

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