| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Dendritic cells (DC) in the stem cell graft can affect the clinical outcome after stem cell transplantation. The use of granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization can also mobilize DCs concurrently. However, the kinetics and functions of DCs induced in the circulation by G-CSF are not well known. We studied the circulating DC population during G-CSF-induced blood progenitor cell mobilization in normal donors and cancer patients. Circulating DCs were counted by flow cytometric analysis and defined as lineage negative, HLD-DR^+, CD11c^+ (DC1) or lineage negative, HLA-DR^+, CD123^+ (DC2). Further, the functions of DCs isolated from stem cell products were studied in vitro. The total number of DCs mobilized significantly increased 4-fold for DC1 and 6-fold for DC2 in normal donors, whereas these respective increases were 3-fold and 5-fold in cancer patients. The DC1/DC2 ratio was reversed in all subjects during G-CSF administration. A lower incidence of DCs, especially DC2, was observed in cancer patients compared to normal donors. Circulatory DCs showed an immature phenotype without the expression of CD80, CD83, or CD86, and functionally were unable to stimulate naive T cells, although they could phagocytose antigens. The administration of G-CSF could be associated with increased circulating DC, especially DC2, and the timing of DC harvest appears to be optimal on day 4 of G-CSF administration, i.e., concurrent with PBSC harvest. Sufficient amounts of DCs can also be harvested following G-CSF administration for tumor vaccination purposes. The skewed DC1/DC2 balance in grafts in autologous and allogeneic settings should be evaluated in further studies.
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