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Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 7 (April 1), 1999: pp. 2244-2252 Long-Term Culture of Human CD34+ Progenitors With FLT3-Ligand, Thrombopoietin, and Stem Cell Factor Induces Extensive Amplification of a CD34CD14 and a CD34CD14+ Dendritic Cell Precursor Jean-François Arrighi, Conrad Hauser, Bernard Chapuis, Rudolf H. Zubler, and Vincent Kindler From the Department of Dermatology and Allergy Unit, the Division of Immunology and Allergy, and the Division of Hematology, Geneva University Hospital, Geneva, Switzerland. Current in vitro culture systems allow the generation of human dendritic cells (DCs), but the output of mature cells remains modest. This contrasts with the extensive amplification of hematopoietic progenitors achieved when culturing CD34+ cells with FLT3-ligand and thrombopoietin. To test whether such cultures contained DC precursors, CD34+ cord blood cells were incubated with the above cytokines, inducing on the mean a 250-fold and a 16,600-fold increase in total cell number after 4 and 8 weeks, respectively. The addition of stem cell factor induced a further fivefold increase in proliferation. The majority of the cells produced were CD34CD1a CD14+ (p14+) and CD34CD1aCD14 (p14) and did not display the morphology, surface markers, or allostimulatory capacity of DC. When cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), both subsets differentiated without further proliferation into immature (CD1a+, CD14, CD83) macropinocytic DC. Mature (CD1a+, CD14, CD83+) DCs with high allostimulatory activity were generated if such cultures were supplemented with tumor necrosis factor- (TNF). In addition, p14 cells generated CD14+ cells with GM-CSF and TNF, which in turn, differentiated into DC when exposed to GM-CSF and IL-4. Similar results were obtained with frozen DC precursors and also when using pooled human serum AB+ instead of bovine serum, emphasizing that this system using CD34+ cells may improve future prospects for immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Stec, K. Weglarczyk, J. Baran, E. Zuba, B. Mytar, J. Pryjma, and M. Zembala Expansion and differentiation of CD14+CD16 and CD14++CD16+ human monocyte subsets from cord blood CD34+ hematopoietic progenitors J. Leukoc. Biol., September 1, 2007; 82(3): 594 - 602. [Abstract] [Full Text] [PDF] S. J. A. M. Santegoets, A. J. Masterson, P. C. van der Sluis, S. M. Lougheed, D. M. Fluitsma, A. J. M. van den Eertwegh, H. M. Pinedo, R. J. Scheper, and T. D. de Gruijl A CD34+ human cell line model of myeloid dendritic cell differentiation: evidence for a CD14+CD11b+ Langerhans cell precursor J. Leukoc. Biol., December 1, 2006; 80(6): 1337 - 1344. 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