Ex Vivo Expansion of Human Primitive Hemopoietic Progenitors

  • Tatsutoshi Nakahata
  • Xingwei Sui
  • Sakura Tajima
  • Kohichiro Tsuji
  • Kiyoshi Yasukawa
  • Tetsuya Taga
  • Tadamitsu Kishimoto


The hemopoietic system is characterized by continuous cell turnover supported by a small populations of cells termed hemopoietic stem cells. It is generally held that multipotential hemopoietic stem cells possess extensive capabilities to self-renew and generate various committed progenitor cells(1). Intercellular communication in the hemopoietic system is mediated by soluble factors called cytokines, whose functional characteristics are now partly explained by their receptor system (2–5). Most cytokine receptor systems consist of a multi-chain complex, a ligand-specific receptor chain (α-chain) and a signal transducing chain (β-chain), the latter of which is often utilized in common by several receptor complexes(2,6).


Human CD34 Hemopoietic Stem Cell Hemopoietic Progenitor Hemopoietic System Signal Transduce Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Ogawa, M.:Differention and proliferation of hematopoietic stem cells. Blood 81, 2844, 1993.PubMedGoogle Scholar
  2. 2.
    Kishimoto, T., Taga, T. & Akira, S.:Cytokine signal transduction. Cell 76, 253, 1994.PubMedCrossRefGoogle Scholar
  3. 3.
    Miyajima, A., Kitamura, T., Harada, N., Yokota, T. & Arai, K.: Cytokine receptors and signal transduction. Ann. Rev. Immunol. 10, 295, 1992.CrossRefGoogle Scholar
  4. 4.
    Stahl, N. & Yancopoulos, G.D.:The alphas, betas, and kinases of cytokine receptor complexes. Cell 74, 587, 1993.PubMedCrossRefGoogle Scholar
  5. 5.
    Metcalf, D.: Hematopoietic regulators: redundancy or subtlety. Blood 82, 3515, 1993.PubMedGoogle Scholar
  6. 6.
    Taga,T. & Kishimoto, T.: Signaling mechanism through cytokine receptors that share signal transducing receptor components. Current Opinion in Immunology 7, 17, 1995.PubMedCrossRefGoogle Scholar
  7. 7.
    Hibi, M., Murakami, M., Satio, M., Hirano, T., Taga, T., & Kishimoto, T.: Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63, 1149, 1990.PubMedCrossRefGoogle Scholar
  8. 8.
    Saito, M., Yoshida, K., Hibi, M., Taga, T. & Kishimoto, T.: Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo. J. Immuno. 148, 4066, 1992.Google Scholar
  9. 9.
    Koike, K., T. Nakahata, T. Takagi, T. Kobayashi, A. Ishiguro, K. Tsuji, K. Naganuma, A. Okano, Y. Akiyama, and T. Akabane.: Synergism of BSF-2/interlukin 6 and interlukin 3 on development of multi-potential hemopoietic progeniotrs in serum-free culture. J. Exp. Med. 168: 879, 1988.PubMedCrossRefGoogle Scholar
  10. 10.
    Sui X, Tsuji K, Tanaka R, Tajima S, Muraoka K, Ebihara Y, Ikebuchi K, Yasukawa K, Taga T, Kishimoto T, Nakahata T.: gp130 and c-Kit 62 signalings synergize for ex vivo expansion of human primitive hemopoietic progenitor cells. Proc. Natl. Acad. Sci. USA 92: 2859, 1995.PubMedCrossRefGoogle Scholar
  11. 11.
    Sui X, Tsuji K, Tajima S, Tanaka R, Muraoka K, Ebihara Y, Ikebuchi K, Yasukawa K, Taga T, Kishimoto T, Nakahata T Erythropoietinindependent erythrocyte production: signals through gp130 and c-Kit dramatically promote erythropoiesis from human CD34+ cells. J. Exp. Med. in press.Google Scholar
  12. 12.
    Yoshida K, Chambers I, Nichols J, Smith A, Saito M, Yasukawa K, Shoyab M, Taga T, Kishimoto T.: Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gpl 30 signaling pathways. Mech. Dev. 45: 163, 1994.PubMedCrossRefGoogle Scholar
  13. 13.
    Yoshida K, Taga T, Saito M, Suematsu S, Kumanogoh A, Tanaka T, Fujiwara H, Hirata M, Yamagami T, Nakahata T, Hirabayashi T, Yoneda Y, Tanaka K, Wang WZ, Mori C, Shiota K, Yoshida N, and Kishimoto T Targeted disruption of gp130, a common signal transducer for IL-6-family of cytokines, leads to myocardial and hematological disorders. Proc. Natl. Acad. Sci. USA in press.Google Scholar
  14. 14.
    Russell ES: Hereditary anemias of the mouse: a review for genetics. Adv. Genet. 20: 357, 1979.PubMedCrossRefGoogle Scholar
  15. 15.
    Honda M, Yamamoto S, Cheng M, Yasukawa K, Suzuki H, Saito T, Osugi Y, Tokunaga T, Kishimoto T.: Human soluble IL-6 receptor, its detection and enhanced release by HIV infection. J. Immunol. 148: 2175, 1992.PubMedGoogle Scholar
  16. 16.
    Lanley KE, Bennett LG, Wypych J, Yancik SA, Liu XD, Westcott KR, Chang WD, Smith KA, Zsebo KM.: Soluble stem cell factor in human serum. Blood 81: 656, 1993.Google Scholar
  17. 17.
    Montero-Julian FA, Liautard J, Flavetta S, Romagne F, Gaillard JP, Brochier J, Klein B, Brailly H.: Immunoassay for functional human soluble interleukin-6 receptor in plasma based on ligand/receptor interactions. J. Immuno. Methods 169: 111, 1994.Google Scholar

Copyright information

© Springer-Verlag Tokyo 1996

Authors and Affiliations

  • Tatsutoshi Nakahata
    • 1
  • Xingwei Sui
    • 2
  • Sakura Tajima
    • 2
  • Kohichiro Tsuji
    • 2
  • Kiyoshi Yasukawa
    • 3
  • Tetsuya Taga
    • 4
  • Tadamitsu Kishimoto
    • 5
  1. 1.Department of Clinical Oncology, The Institute of Medical ScienceThe University of TokyoMinato-ku Tokyo 108Japan
  2. 2.Department of Clinical Oncology The Institute of Medical ScienceThe University of TokyoMinato-ku Tokyo 108Japan
  3. 3.Biotechnology Research LaboratoryTOSOH CorporationAyase, Kanagawa 252Japan
  4. 4.Institute for Molecular and Cellular BiologyOsaka UniversitySuita, Osaka 565Japan
  5. 5.Department of Medicine IIIOsaka University Medical SchoolSuita, Osaka 565Japan

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