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Type: Journal article
Title: EphB4 expressing stromal cells exhibit an enhanced capacity for hematopoietic stem cell maintenance
Author: Nguyen, T.
Arthur, A.
Panagopoulos, R.
Paton, S.
Hayball, J.
Zannettino, A.
Purton, L.
Matsuo, K.
Gronthos, S.
Citation: Stem Cells, 2015; 33(9):2838-2849
Publisher: Wiley
Issue Date: 2015
ISSN: 1066-5099
Statement of
Thao M. Nguyen, Agnieszka Arthur, Romana Panagopoulos, Sharon Paton, John D. Hayball, Andrew C.W. Zannettino, Louise E. Purton, Koichi Matsuo, and Stan Gronthos
Abstract: The tyrosine kinase receptor, EphB4, mediates cross-talk between stromal and hematopoietic populations during bone remodeling, fracture repair and arthritis, through its interactions with the ligand, ephrin-B2. This study demonstrated that transgenic EphB4 mice (EphB4 Tg), over-expressing EphB4 under the control of collagen type-1 promoter, exhibited higher frequencies of osteogenic cells and hematopoietic stem/progenitor cells (HSC), correlating with a higher frequency of long-term culture-initiating cells (LTC-IC), compared with wild type (WT) mice. EphB4 Tg stromal feeder layers displayed a greater capacity to support LTC-IC in vitro, where blocking EphB4/ephrin-B2 interactions decreased LTC-IC output. Similarly, short hairpin RNA-mediated EphB4 knockdown in human bone marrow stromal cells reduced their ability to support high ephrin-B2 expressing CD34⁺ HSC in LTC-IC cultures. Notably, irradiated EphB4 Tg mouse recipients displayed enhanced bone marrow reconstitution capacity and enhanced homing efficiency of transplanted donor hematopoietic stem/progenitor cells relative to WT controls. Studies examining the expression of hematopoietic supportive factors produced by stromal cells indicated that CXCL12, Angiopoietin-1, IL-6, FLT-3 ligand, and osteopontin expression were more highly expressed in EphB4 Tg stromal cells compared with WT controls. These findings indicate that EphB4 facilitates stromal-mediated support of hematopoiesis, and constitute a novel component of the HSC niche.
Keywords: Haematopoietic stem cells; bone marrow stromal cells; EphB; ephrinB; mesenchymal stem cells
Rights: © AlphaMed Press 2015
DOI: 10.1002/stem.2069
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