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https://hdl.handle.net/2440/100245
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dc.contributor.author | Nguyen, T. | - |
dc.contributor.author | Arthur, A. | - |
dc.contributor.author | Panagopoulos, R. | - |
dc.contributor.author | Paton, S. | - |
dc.contributor.author | Hayball, J. | - |
dc.contributor.author | Zannettino, A. | - |
dc.contributor.author | Purton, L. | - |
dc.contributor.author | Matsuo, K. | - |
dc.contributor.author | Gronthos, S. | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Stem Cells, 2015; 33(9):2838-2849 | - |
dc.identifier.issn | 1066-5099 | - |
dc.identifier.issn | 1549-4918 | - |
dc.identifier.uri | http://hdl.handle.net/2440/100245 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | Thao M. Nguyen, Agnieszka Arthur, Romana Panagopoulos, Sharon Paton, John D. Hayball, Andrew C.W. Zannettino, Louise E. Purton, Koichi Matsuo, and Stan Gronthos | - |
dc.language.iso | en | - |
dc.publisher | Wiley | - |
dc.rights | © AlphaMed Press 2015 | - |
dc.source.uri | http://dx.doi.org/10.1002/stem.2069 | - |
dc.subject | Haematopoietic stem cells; bone marrow stromal cells; EphB; ephrinB; mesenchymal stem cells | - |
dc.title | EphB4 expressing stromal cells exhibit an enhanced capacity for hematopoietic stem cell maintenance | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1002/stem.2069 | - |
dc.relation.grant | http://purl.org/au-research/grants/nhmrc/1023390 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Nguyen, T. [0000-0001-9066-6962] | - |
dc.identifier.orcid | Arthur, A. [0000-0002-0539-8797] | - |
dc.identifier.orcid | Paton, S. [0000-0001-7031-3510] | - |
dc.identifier.orcid | Hayball, J. [0000-0002-3089-4506] | - |
dc.identifier.orcid | Zannettino, A. [0000-0002-6646-6167] | - |
dc.identifier.orcid | Gronthos, S. [0000-0002-6225-3084] | - |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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