Unilineage monocytopoiesis in hematopoietic progenitor culture: switching cytokine treatment at all Mo developmental stages induces differentiation into dendritic cells

We have developed a new culture system whereby human hematopoietic progenitors purified from adult peripheral blood extensively proliferate and gradually differentiate into >95% pure monocytic (Mo) cells. At all developmental stages treatment with interleukin (IL)-4+granulocyte-macrophage colony-...

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Veröffentlicht in:Cell death and differentiation 2006-02, Vol.13 (2), p.250-259
Hauptverfasser: Montesoro, E, Castelli, G, Morsilli, O, Nisini, R, Stafsnes, M H, Carè, A, Peschle, C, Chelucci, C
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container_end_page 259
container_issue 2
container_start_page 250
container_title Cell death and differentiation
container_volume 13
creator Montesoro, E
Castelli, G
Morsilli, O
Nisini, R
Stafsnes, M H
Carè, A
Peschle, C
Chelucci, C
description We have developed a new culture system whereby human hematopoietic progenitors purified from adult peripheral blood extensively proliferate and gradually differentiate into >95% pure monocytic (Mo) cells. At all developmental stages treatment with interleukin (IL)-4+granulocyte-macrophage colony-stimulating factor or IL-4+c-Kit-ligand+FLT-3 ligand switched the Mo precursors into dendritic cells (DCs). The switching capacity decreased only at the end of the culture, when most Mo cells matured to macrophages. Moreover, the Mo precursors were highly susceptible to transduction with lentiviral vectors: once switched to DCs, they maintained the transgene expression, as well as the phenotype and function of the DC lineage. Our results provide new insight into the potential role of the Mo lineage as a reservoir of DCs in vivo . Furthermore, the methodology for transduction of Mo precursors provides a tool to generate genetically modified, normally functioning DCs potentially useful for immunotherapy.
doi_str_mv 10.1038/sj.cdd.4401748
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subjects Antigens
Apoptosis
Biochemistry
Biomedical and Life Sciences
Bone marrow
Cell Biology
Cell Cycle Analysis
Cell death
Cell growth
Cell Lineage
Cell Proliferation - drug effects
Cells, Cultured
Cytokines
Cytokines - pharmacology
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - physiology
Gene Expression Regulation
Gene Transfer Techniques
Genetic Vectors
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Granulocytes
Hematology
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - drug effects
Humans
Immunotherapy
Interleukin-4 - pharmacology
Lentivirus - genetics
Leukocytes
Life Sciences
Ligands
Membrane Proteins - pharmacology
Monocytes - chemistry
Monocytes - cytology
Monocytes - drug effects
Myelopoiesis - drug effects
Oncology
original-paper
Phenotype
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - analysis
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Stem Cell Factor - pharmacology
Stem Cells
Transduction, Genetic
Transgenes
Tumor necrosis factor-TNF
title Unilineage monocytopoiesis in hematopoietic progenitor culture: switching cytokine treatment at all Mo developmental stages induces differentiation into dendritic cells
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