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LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance

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Abstract

The nonhematopoietic bone marrow (BM) microenvironment provides a functional niche for hematopoietic cell maintenance, recruitment, and differentiation. It consists of multiple cell types including vasculature, bone, adipose tissue, and fibroblast-like bone marrow stromal cells (BMSC), which can be summarized under the generic term niche cells. BMSC express Toll-like receptors (TLRs) and are capable to respond to TLR-agonists by changing their cytokine expression pattern in order to more efficiently support hematopoiesis. Here, we show that in addition to enhanced myeloid colony formation from human CD34+ cells, lipopolysaccharide (LPS) stimulation retains overall higher numbers of CD34+ cells in co-culture assays using BMSC, with eightfold more CD34+ cells that underwent up to three divisions as compared to non-stimulated assays. When subjected to cytokine-supplemented myeloid colony-forming unit (CFU) assays or transplanted into newborn RAG2−/− γc −/− mice, CD34+ cells from LPS-stimulated BMSC cultures give rise to the full spectrum of myeloid colonies and T and B cells, respectively, thus supporting maintenance of myeloid and lymphoid primed hematopoietic progenitor cells (HPCs) under inflammatory conditions. Collectively, we suggest that BMSC enhance hematopoiesis during inflammatory conditions to support the replenishment of innate immune effector cells and to prevent the exhaustion of the hematopoietic stem and progenitor cell (HSPC) pool.

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    Authors and Affiliations

    1. Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany

      Patrick Ziegler

    2. Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, 6500, Bellinzona, Switzerland

      Patrick Ziegler, Steffen Boettcher, Hitoshi Takizawa & Markus G. Manz

    3. Division of Hematology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland

      Steffen Boettcher, Hitoshi Takizawa & Markus G. Manz

    4. Department of Oncology, Hematology, Hemostaseology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany

      Tim H. Brümmendorf

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    1. Patrick Ziegler
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    2. Steffen Boettcher
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    3. Hitoshi Takizawa
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    4. Markus G. Manz
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    Correspondence to Patrick Ziegler.

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    The authors declare no conflict of interest. All authors have read the journal’s authorship agreement and policy on disclosure of potential conflicts of interest.

    Funding

    This work was in part funded by a START grant of the Medical faculty of RWTH Aachen University to P.Z.

    Additional information

    Markus G. Manz and Tim H. Brümmendorf contributed equally to this work.

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    Ziegler, P., Boettcher, S., Takizawa, H. et al. LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance. Ann Hematol 95, 173–178 (2016). https://doi.org/10.1007/s00277-015-2550-5

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    • DOI: https://doi.org/10.1007/s00277-015-2550-5

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