Nguyen, T.Arthur, A.Panagopoulos, R.Paton, S.Hayball, J.Zannettino, A.Purton, L.Matsuo, K.Gronthos, S.2016-07-272016-07-272015Stem Cells, 2015; 33(9):2838-28491066-50991549-4918http://hdl.handle.net/2440/100245The 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.en© AlphaMed Press 2015Haematopoietic stem cells; bone marrow stromal cells; EphB; ephrinB; mesenchymal stem cellsJournal article003003021710.1002/stem.20690003600189000172-s2.0-849404671992-s2.0-84932084929188122Nguyen, T. [0000-0001-9066-6962]Arthur, A. [0000-0002-0539-8797]Paton, S. [0000-0001-7031-3510]Hayball, J. [0000-0002-3089-4506]Zannettino, A. [0000-0002-6646-6167]Gronthos, S. [0000-0002-6225-3084]