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Expansion of dendritic cell precursors from human CD34 + progenitor cells isolated from healthy donor blood; growth factor combination determines proliferation rate and functional outcome
Author(s) -
Bontkes Hetty J.,
Gruijl Tanja D.,
Schuurhuis Gert Jan,
Scheper Rik J.,
Meijer Chris J. L. M.,
Hooijberg Erik
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.2.321
Subject(s) - stem cell factor , biology , haematopoiesis , cd34 , cytotoxic t cell , progenitor cell , dendritic cell , priming (agriculture) , cytokine , microbiology and biotechnology , interleukin 3 , stem cell , immunology , antigen presenting cell , cancer research , t cell , antigen , immune system , in vitro , biochemistry , botany , germination
CD34 + haematopoietic progenitor cells, which circulate at extremely low frequencies in peripheral blood, are used to generate dendritic cells (DC) in vitro. Here, we describe a method to grow large numbers of DC precursors from these low frequent cells. Different combinations of early acting haematopoietic growth factors supported expansion of CD34 + cells. CD1a + DC derived from precursors, expanded in fms ‐like tyrosine kinase‐3 ligand (Flt3‐L), stem‐cell factor (SCF), interleukin (IL)‐3, and IL‐6, were less potent antigen‐presenting cells (APC) compared to CD1a + DC derived from precursors expanded in Flt3‐L, trombopoietine (TPO), and SCF. Furthermore, the latter produced high levels of IL‐12 and low levels of IL‐10, a cytokine profile favorable for the priming cytotoxic T cells. In contrast, a mean increase of total cell number of 453‐fold was obtained with Flt3‐L, SCF, IL‐3, and IL‐6, and this increase was only 38‐fold with Flt3‐L, TPO, and SCF. Sequential cultures of both cocktails resulted in high numbers of potent APC, which can be useful DC‐based cancer vaccines.