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

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• 作者：Patrick Ziegler ; Steffen Boettcher ; Hitoshi Takizawa…
• 关键词：Bone marrow stroma cells ; Niche ; Inflammation ; LPS
• 刊名：Annals of Hematology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：95
• 期：2
• 页码：173-178
• 全文大小：532 KB
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• 作者单位：Patrick Ziegler (1) (2)
  Steffen Boettcher (2) (3)
  Hitoshi Takizawa (2) (3)
  Markus G. Manz (2) (3)
  Tim H. Brümmendorf (4)
  
  1. Institute for Occupational and Social Medicine, RWTH Aachen University, Aachen, Germany
  2. Institute for Research in Biomedicine (IRB), Via Vincenzo Vela 6, 6500, Bellinzona, Switzerland
  3. Division of Hematology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland
  4. Department of Oncology, Hematology, Hemostaseology and Stem cell transplantation, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Hematology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0584

文摘

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−/− γ_c −/− 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.