Splenic stromal niches support hematopoiesis of dendritic-like cells from precursors in bone marrow and spleen

Periasamy, Pravin; Tan, Jeff; Griffiths, Kristin; O’Neill, Helen C.

doi:10.1016/j.exphem.2009.06.001

Cited by 44 publications

(157 citation statements)

References 27 publications

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“…The possibility that the L-DC progenitor is endogenous to spleen is supported by evidence that blood does not contain precursors, which seed cocultures for L-DC production. 24,25 Although adult Lin Ϫ c-kit ϩ spleen progenitors produce specifically L-DCs in cocultures, this restricted development was not replicated in vivo. This indicates a limitation of stroma for supporting only the development of L-DCs from overlaid spleen or BM cells.…”

Section: Discussionmentioning

confidence: 99%

“…Overlaid whole BM, known to produce DCs in coculture over STX3 stroma, 21,24,25 was used as a positive control. Initially, spleen cells were depleted of T and B cells and then sorted on the basis of c-kit and CD11c expression, to yield c-kit Ϫ CD11c Ϫ and c-kit ϩ CD11c Ϫ subsets for comparison (Figure 2A).…”

Section: Characterization Of L-dc Precursors In Spleenmentioning

confidence: 99%

“…[20][21][22][23] Cloned stromal cell lines support production of distinct dendritic-like cells from precursors contained within BM and spleen equivalent to those produced in LTCs. 24,25 These have been tentatively named L-DCs. 24 This paper characterizes precursors present in spleen that produce L-DCs in coculture over splenic endothelial stroma.…”

Section: Introductionmentioning

confidence: 99%

“…24,25 These have been tentatively named L-DCs. 24 This paper characterizes precursors present in spleen that produce L-DCs in coculture over splenic endothelial stroma. Identification of these cells was based on previous evidence that the small cell population of LTCs contained cells expressing c-kit and Sca1.…”

Section: Introductionmentioning

confidence: 99%

“…When allogeneic or syngeneic spleen or BM cells were cocultured over STX3, only myeloid dendritic-like cells were produced. 24,25 To establish cocultures, STX3 stroma was grown to 80% to 90% confluence before addition of overlay cells at 1 to 5 ϫ 10 5 cells/mL. For coculture maintenance, half medium was exchanged every 3 to 4 days.…”

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confidence: 99%

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Delineation of precursors in murine spleen that develop in contact with splenic endothelium to give novel dendritic-like cells

Tan

Periasamy

O’Neill

2010

Blood

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IntroductionDendritic cells (DCs) are specialized antigen-presenting cells, which capture and process peripheral antigens for presentation to naive T cells. 1 They exist in peripheral tissues as immature cells, displaying characteristics optimal for antigen uptake and surveillance of local environments. Under these conditions, they present apoptotic self cells to T cells to maintain peripheral tolerance. 2,3 On exposure to pathogens, DCs can also become immunogenic, adopting a mature, activated phenotype, a state distinct by additional secretion of proinflammatory cytokines, such as interleukin-12, which promote effector T-cell differentiation. 4 Multiple DC subsets are present in tissues around the body, and in spleen the main subsets include conventional DCs (cDCs) and plasmacytoid DCs (pDCs). cDCs are represented by 2 main populations of CD8␣ Ϫ and CD8␣ ϩ cDC. Morphologically, cDCs are small, nongranular cells 5 that express high levels of CD11c and major histocompatibility complex class II (MHC-II) markers. 6 pDCs are a distinct subset characterized by a small and plasmacytoid morphology, and a pronounced capacity to secrete high levels of IFN-␣ on viral stimulation. 7,8 Isolating rare DC subsets for experimentation is a difficult task, and the isolation and study of DC precursors represent an even more challenging area. It is, however, necessary to delineate precursors to perform lineage experiments to define their downstream progeny. Indeed, examination of DC precursors from early granulocyte-macrophage colony-stimulating factor/interleukin-4 cytokine culture systems has not been possible because of the enforced maturation of precursors. 9,10 Recently, improved cultures of bone marrow (BM) cells with Fms-like tyrosine kinase 3 ligand (Flt3-L) have facilitated the study of DC development, 11,12 with in vitro identification of 2 sequential cDC precursors CD11c int CD115 ϩ c-kit Ϫ pre-DCs and CD11c Ϫ CD115 ϩ c-kit int proDCs. 13 Furthermore, in vivo counterparts of pre-DCs have been identified in spleen as CD11c int CD43 int SIRP-␣ int cells, 14 and counterparts to pro-DC have been identified as Lin Ϫ c-kit lo Flt3 ϩ cells, present in BM but not spleen. 15 Success in these studies highlights the value of in vitro culture systems for investigating DC development from precursors.Previously, development of dendritic-like cells in spleen longterm cultures (LTCs) was demonstrated, which was unique in relation to other culture systems producing DCs. Cultures are continuous, maintaining 2 cell populations distinct in size as "small" and "large" cells. 16 Large cells were previously characterized as a homogeneous population of immature myeloid dendriticlike CD11c lo CD11b hi CD8 Ϫ MHC-II Ϫ/lo cells, named LTC-DCs. These were highly endocytic and weakly able to present antigen to CD4 ϩ T cells. 17,18 The identity of a precursor within the small cell population was resolved by sorting and coculturing small cells above a spleen stromal cell line, which supports LTC-DC development. 16 This resulted in development of larg...

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Section: Discussionmentioning

confidence: 99%

Section: Characterization Of L-dc Precursors In Spleenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Delineation of precursors in murine spleen that develop in contact with splenic endothelium to give novel dendritic-like cells

Tan

Periasamy

O’Neill

2010

Blood

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Targeting the Spleen as an Alternative Site for Hematopoiesis

et al. 2019

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Bone marrow is the main site for hematopoiesis in adults. It acts as a niche for hematopoietic stem cells (HSCs) and contains non‐hematopoietic cells that contribute to stem cell dormancy, quiescence, self‐renewal, and differentiation. HSC also exist in resting spleen of several species, although their contribution to hematopoiesis under steady‐state conditions is unknown. The spleen can however undergo extramedullary hematopoiesis (EMH) triggered by physiological stress or disease. With the loss of bone marrow niches in aging and disease, the spleen as an alternative tissue site for hematopoiesis is an important consideration for future therapy, particularly during HSC transplantation. In terms of harnessing the spleen as a site for hematopoiesis, here the remarkable regenerative capacity of the spleen is considered with a view to forming additional or ectopic spleen tissue through cell engraftment. Studies in mice indicate the potential for such grafts to support the influx of hematopoietic cells leading to the development of normal spleen architecture. An important goal will be the formation of functional ectopic spleen tissue as an aid to hematopoietic recovery following clinical treatments that impact bone marrow. For example, expansion or replacement of niches could be considered where myeloablation ahead of HSC transplantation compromises treatment outcomes.

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Extramedullary hematopoiesis: mesenchymal stromal cells from spleen provide an in vitro niche for myelopoiesis

Petvises

Tran

Hey

et al. 2022

In Vitro Cell.Dev.Biol.-Animal

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Murine spleen has been shown to harbour stromal cells that support hematopoiesis with production of myeloid antigen–presenting cells. Similar stromal lines have now been isolated from long-term cultures (LTC) of human spleen. When human progenitor populations from spleen, bone marrow and cord blood were employed as a source of progenitors for co-culture above splenic stromal lines, myelopoiesis was supported. Human splenocytes gave production of predominantly myeloid dendritic-like cells, with minor subsets resembling conventional dendritic cells (cDC) cells, and myeloid or monocyte-derived DC. Human bone marrow progenitors gave rise to myelopoiesis from hematopoietic progenitors, while human cord blood supported limited myelopoiesis from existing myeloid precursors. Transcriptome analysis compared two stromal lines differing in myelopoietic support capacity. Gene profiling revealed both stromal lines to reflect perivascular reticular cells with osteogenic characteristics. However, the 5C6 stroma which failed to support hematopoiesis uniquely expressed several inhibitors of the WNT pathway. Combined data now show that splenic stroma of both human and murine origin provides a mesenchymal stromal cell microenvironment which is WNT pathway–dependent, and which supports in vitro myelopoiesis with production of specific subsets of myeloid and dendritic-like cells.

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Splenic stromal niches support hematopoiesis of dendritic-like cells from precursors in bone marrow and spleen

Cited by 44 publications

References 27 publications

Delineation of precursors in murine spleen that develop in contact with splenic endothelium to give novel dendritic-like cells

Delineation of precursors in murine spleen that develop in contact with splenic endothelium to give novel dendritic-like cells

Targeting the Spleen as an Alternative Site for Hematopoiesis

Extramedullary hematopoiesis: mesenchymal stromal cells from spleen provide an in vitro niche for myelopoiesis

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