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 journalArticlepeer-review

8 Citations (Scopus)

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

All Science Journal Classification (ASJC) codes

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

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