Flt3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells: Possible application for cancer immunotherapy

  • Authors:
    • Sachio Harada
    • Takafumi Kimura
    • Hiroshi Fujiki
    • Hitoshi Nakagawa
    • Yuji Ueda
    • Tsuyoshi Itoh
    • Hisakazu Yamagishi
    • Yoshiaki Sonoda
  • View Affiliations

  • Published online on: June 1, 2007     https://doi.org/10.3892/ijo.30.6.1461
  • Pages:1461-1468
0

Abstract

Current in vitro culture systems allow the generation of human dendritic progenitor cells (CFU-DCs). The aim of this study was to assess the effect of Flt3 ligand (FL) on the proliferation of human peripheral blood-derived myeloid CFU-DCs and their differentiation into more committed precursor cells (pDCs) using in vitro culture systems. Immunomagnetically separated CD34+ cells were cultured in serum-free, as well as in serum-containing, liquid suspension cultures to investigate the expansion and/or proliferation/differentiation of CFU-DCs, pDCs, and more mature dendritic cells (DCs). FACS-sorted CD34+Flt3+/− cells were cultured in methylcellulose to assay hematopoietic progenitors, including CFU-DCs. In the clonal cell culture supplemented with granulocyte/macrophage (GM) colony-stimulating factor (CSF), interleukin-4, and tumor necrosis factor α, the frequency of CFU-DCs was significantly higher in the CD34+Flt3+ fraction than in the CD34+Flt3− population, thus suggesting functional Flt3 expression on CFU-DCs. Serum-free suspension culture of CD34+ cells revealed the potent effect of FL on the expansion of CFU-DCs in synergy with GM-CSF and thrombopoietin (TPO). In addition, FL strongly induced the maturation of CFU-DCs into functional CD1a+ pDCs in serum-containing liquid suspension culture. Moreover, these FL-generated pDCs showed remarkable potential to differentiate into mature DCs with surface CD83/CD86 expression, which induced a distinct allogeneic T-cell response. These results clearly demonstrate that FL supports not only the proliferation of early hematopoietic progenitor cells, but also the maturation process of committed precursor cells along with the DC-lineage differentiation. Therefore, it is possible to develop a more efficient DC-based cancer immunotherapy using this specific cytokine combination, GM-CSF+TPO+FL in vitro in the near future.

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June 2007
Volume 30 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2015 Impact Factor: 3.018
Ranked #30/211 Oncology
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APA
Harada, S., Kimura, T., Fujiki, H., Nakagawa, H., Ueda, Y., Itoh, T. ... Sonoda, Y. (2007). Flt3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells: Possible application for cancer immunotherapy. International Journal of Oncology, 30, 1461-1468. https://doi.org/10.3892/ijo.30.6.1461
MLA
Harada, S., Kimura, T., Fujiki, H., Nakagawa, H., Ueda, Y., Itoh, T., Yamagishi, H., Sonoda, Y."Flt3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells: Possible application for cancer immunotherapy". International Journal of Oncology 30.6 (2007): 1461-1468.
Chicago
Harada, S., Kimura, T., Fujiki, H., Nakagawa, H., Ueda, Y., Itoh, T., Yamagishi, H., Sonoda, Y."Flt3 ligand promotes myeloid dendritic cell differentiation of human hematopoietic progenitor cells: Possible application for cancer immunotherapy". International Journal of Oncology 30, no. 6 (2007): 1461-1468. https://doi.org/10.3892/ijo.30.6.1461