Open AccessDendritic Cell Development in Long‐Term Spleen Stromal Cultures
Author(s) -
O'Neill Helen C.,
Wilson Heather L.,
Quah Ben,
Abbey Janice L.,
Despars Geneviève,
Ni Keping
Publication year - 2004
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.22-4-475
Subject(s) - biology , progenitor cell , haematopoiesis , microbiology and biotechnology , stromal cell , bone marrow , stem cell , immunology , dendritic cell , population , spleen , cd34 , cancer research , immune system , medicine , environmental health
The cellular microenvironments in which dendritic cells (DCs) develop are not known. DCs are commonly expanded from CD34 + bone marrow precursors or blood monocytes using a cocktail of growth factors including GM‐CSF. However, cytokine‐supported cultures are not suitable for studying the intermediate stages of DC development, since progenitors are quickly driven to become mature DCs that undergo limited proliferation and survive for only a short period of time. This lab has developed a long‐term culture (LTC) system from spleen which readily generates a high yield of DCs. Hematopoietic cells develop under more normal physiological conditions than in cultures supplemented with cytokines. A spleen stromal cell monolayer supports stem cell maintenance, renewal, and the specific differentiation of only DCs and no other hematopoietic cells. Cultures maintain continuous production of a small population of small‐sized progenitors and a large population of fully developed DCs. Cell–cell interaction between stromal cells and progenitor cells is critical for DC differentiation. The progenitors maintained in LTC appear to be quite distinct from bone marrow–derived DC progenitors that respond to GM‐CSF. The majority of cells produced in LTC are large‐sized cells with a phenotype reflecting myeloid‐like DC precursors or immature DCs. These cells are highly endocytotic and weakly immunostimulatory for T cells. This model system predicts in situ production of DCs in spleen from endogenous progenitors, as well as a central role for spleen in DC hematopoiesis.