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Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin‐12 production by mature dendritic cells
Author(s) -
Van Den Berk Lieke C. J.,
Roelofs Helene,
Huijs Tonnie,
SiebersVermeulen Kim G. C.,
Raymakers Reinier A.,
Kögler Gesine,
Figdor Carl G.,
Torensma Ruurd
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03142.x
Subject(s) - microbiology and biotechnology , mesenchymal stem cell , follicular dendritic cells , stem cell , dendritic cell , biology , haematopoiesis , cord blood , immunology , population , antigen presenting cell , antigen , immune system , t cell , medicine , environmental health
Summary Pathogen‐derived entities force the tissue‐resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord blood an immature MSC population was identified. Remarkably, these immature stem cells modulated DCs in a different way. Marker expression was unchanged during the differentiation of monocytes towards immature DCs (iDCs) when cocultured with cord blood MSC [unrestricted somatic stem cells (USSCs)]. The maturation to mature DCs (mDCs) was enhanced when DCs were co‐cultured with USSC, as evidenced by the up‐regulation of costimulatory molecules. Endocytosis of dextran by iDCs was hampered in the presence of USSCs, which is indicative for the maturation of iDCs. Despite this maturation, the migration of iDCs cocultured with USSCs appeared to be identical to iDCs cultured alone. However, USSCs increased the migration of mDCs towards CCL21 and boosted interleukin‐12 production. So, USSCs mature iDCs, thereby redirecting the antigen‐uptake phenotype towards a mature phenotype. Furthermore, DC maturation by lipopolysaccharide (LPS) or USSCs reflects two distinct pathways because migration was unaffected when iDCs were matured by coculture with USSCs, while it was strongly enhanced in the presence of LPS. DCs are able to discriminate the different MSC subtypes, resulting in diverse differentiation programmes.