Dendritic cell development in long-term spleen stromal cultures

Helen C O'Neill, HL Wilson, B Quah, JL Abbey, G Despars, KP Ni

Research output: Contribution to journalReview articleResearchpeer-review

60 Citations (Scopus)

Abstract

The cellular microenvironments in which dendritic cells (DCs) develop are not known. DCs are commonly expanded from CD3(+) 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.

Original languageEnglish
Pages (from-to)475-486
Number of pages12
JournalStem Cells
Volume22
Issue number4
DOIs
Publication statusPublished - 2004
Externally publishedYes

Cite this

O'Neill, H. C., Wilson, HL., Quah, B., Abbey, JL., Despars, G., & Ni, KP. (2004). Dendritic cell development in long-term spleen stromal cultures. Stem Cells, 22(4), 475-486. https://doi.org/10.1634/stemcells.22-4-475
O'Neill, Helen C ; Wilson, HL ; Quah, B ; Abbey, JL ; Despars, G ; Ni, KP. / Dendritic cell development in long-term spleen stromal cultures. In: Stem Cells. 2004 ; Vol. 22, No. 4. pp. 475-486.
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O'Neill, HC, Wilson, HL, Quah, B, Abbey, JL, Despars, G & Ni, KP 2004, 'Dendritic cell development in long-term spleen stromal cultures' Stem Cells, vol. 22, no. 4, pp. 475-486. https://doi.org/10.1634/stemcells.22-4-475

Dendritic cell development in long-term spleen stromal cultures. / O'Neill, Helen C; Wilson, HL; Quah, B; Abbey, JL; Despars, G; Ni, KP.

In: Stem Cells, Vol. 22, No. 4, 2004, p. 475-486.

Research output: Contribution to journalReview articleResearchpeer-review

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AU - Wilson, HL

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AU - Abbey, JL

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AB - The cellular microenvironments in which dendritic cells (DCs) develop are not known. DCs are commonly expanded from CD3(+) 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.

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