Cytokine-based log-scale expansion of functional murine dendritic cells

Yui Harada, Yasuji Ueda, Hiroaki Kinoh, Atsushi Komaru, Terumi Fuji-Ogawa, Aki Furuya, Akihiro Iida, Mamoru Hasegawa, Tomohiko Ichikawa, Yoshikazu Yonemitsu

Research output: Contribution to journalArticle

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Abstract

Background: Limitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies. Methodology/Principal Findings: Floating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines. Conclusions/Significance: The concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy.

Original languageEnglish
Article numbere6674
JournalPLoS One
Volume4
Issue number8
DOIs
Publication statusPublished - Aug 18 2009

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dendritic cells
Dendritic Cells
cytokines
Cytokines
immunotherapy
mice
Immunotherapy
interleukin-3
Cancer Vaccines
Interleukin-3
interleukin-4
Granulocyte-Macrophage Colony-Stimulating Factor
interleukin-6
Interleukin-4
bone marrow
Interleukin-6
cell proliferation
Bone
Bone Marrow
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cytokine-based log-scale expansion of functional murine dendritic cells. / Harada, Yui; Ueda, Yasuji; Kinoh, Hiroaki; Komaru, Atsushi; Fuji-Ogawa, Terumi; Furuya, Aki; Iida, Akihiro; Hasegawa, Mamoru; Ichikawa, Tomohiko; Yonemitsu, Yoshikazu.

In: PLoS One, Vol. 4, No. 8, e6674, 18.08.2009.

Research output: Contribution to journalArticle

Harada, Y, Ueda, Y, Kinoh, H, Komaru, A, Fuji-Ogawa, T, Furuya, A, Iida, A, Hasegawa, M, Ichikawa, T & Yonemitsu, Y 2009, 'Cytokine-based log-scale expansion of functional murine dendritic cells', PLoS One, vol. 4, no. 8, e6674. https://doi.org/10.1371/journal.pone.0006674
Harada Y, Ueda Y, Kinoh H, Komaru A, Fuji-Ogawa T, Furuya A et al. Cytokine-based log-scale expansion of functional murine dendritic cells. PLoS One. 2009 Aug 18;4(8). e6674. https://doi.org/10.1371/journal.pone.0006674
Harada, Yui ; Ueda, Yasuji ; Kinoh, Hiroaki ; Komaru, Atsushi ; Fuji-Ogawa, Terumi ; Furuya, Aki ; Iida, Akihiro ; Hasegawa, Mamoru ; Ichikawa, Tomohiko ; Yonemitsu, Yoshikazu. / Cytokine-based log-scale expansion of functional murine dendritic cells. In: PLoS One. 2009 ; Vol. 4, No. 8.
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