title: LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance.
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.
authors.affiliation: Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany. pziegler@ukaachen.de.|Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, 6500, Bellinzona, Switzerland. pziegler@ukaachen.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
authors.affiliation: Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, 6500, Bellinzona, Switzerland.|Division of Hematology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Steffen
authors.initials: S
authors.lastname: Boettcher
authors.affiliation: Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, 6500, Bellinzona, Switzerland.|Division of Hematology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takizawa
authors.affiliation: Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, 6500, Bellinzona, Switzerland.|Division of Hematology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Manz
authors.affiliation: Department of Oncology, Hematology, Hemostaseology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects / Q000502:physiology*
chemical_list: D018952:Antigens, CD34; D008070:Lipopolysaccharides
keywords: Bone marrow stroma cells; Inflammation; LPS; Niche