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http://hdl.handle.net/2440/100245
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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 1549-4918 |
Statement of Responsibility: | 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 |
RMID: | 0030030217 |
DOI: | 10.1002/stem.2069 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1023390 |
Appears in Collections: | Medicine publications |
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