Spleen stroma maintains progenitors and supports long-term hematopoiesis

Helen C. O'Neill, Kristin L. Griffiths, Pravin Periasamy, Rebecca A. Hinton, Sawang Petvises, Ying ying Hey, Jonathan K.H. Tan

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Hematopoietic stem/progenitor cells (HSPC) differentiate in the context of stromal niches producing cells of multiple lineages. Limited success has been achieved in the past with induction of hematopoiesis in vitro. Previously, spleen long-term stromal cultures (LTC) were shown to continuously support restricted hematopoiesis for production of novel dendritic-like cells (LTC-DC). An in vivo equivalent dendritic cell type was then described which is specific for spleen. The in vivo counterpart cell was termed 'L-DC' and represents a dendritic-like CD11cloCD11bhiCD8α-MHC-II- cell which differs phenotypically and functionally from monocytes/macrophages and conventional and plasmacytoid DC. Splenic stroma is now shown to maintain HSPC and to support their restricted in vitro differentiation to give this 'L-DC' subset. In order to characterise progenitors of this distinct cell type, LTC were analysed for cell subsets produced, and these subsets sorted and assessed for hematopoietic potential in subsequent co-cultures over STX3 stroma. Progenitors were defined as a lineage (Lin)-ckitlo subset reflecting HSPC. Furthermore, when Lin-ckithiSca1+Flt3- HSPC were sorted from bone marrow, they colonised splenic stroma with long-term production of L-DC. The maintenance of HSPC by splenic stroma was confirmed when non-adherent cells collected from LTC showed oligopotent reconstitution of the hematopoietic compartment of lethally irradiated mice. All data support a model whereby spleen houses a niche for HSPC in the resting state, with production of progenitors, and their differentiation to give tissue-specific antigen presenting cells.

    Original languageEnglish
    Pages (from-to)354-363
    Number of pages10
    JournalCurrent Stem Cell Research and Therapy
    Volume9
    Issue number4
    DOIs
    Publication statusPublished - 2014

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