EphB4 expressing stromal cells exhibit an enhanced capacity for hematopoietic stem cell maintenance

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dc.contributor.authorNguyen, T.
dc.contributor.authorArthur, A.
dc.contributor.authorPanagopoulos, R.
dc.contributor.authorPaton, S.
dc.contributor.authorHayball, J.
dc.contributor.authorZannettino, A.
dc.contributor.authorPurton, L.
dc.contributor.authorMatsuo, K.
dc.contributor.authorGronthos, S.
dc.date.issued2015
dc.description.abstractThe 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.statementofresponsibilityThao M. Nguyen, Agnieszka Arthur, Romana Panagopoulos, Sharon Paton, John D. Hayball, Andrew C.W. Zannettino, Louise E. Purton, Koichi Matsuo, and Stan Gronthos
dc.identifier.citationStem Cells, 2015; 33(9):2838-2849
dc.identifier.doi10.1002/stem.2069
dc.identifier.issn1066-5099
dc.identifier.issn1549-4918
dc.identifier.orcidNguyen, T. [0000-0001-9066-6962]
dc.identifier.orcidArthur, A. [0000-0002-0539-8797]
dc.identifier.orcidPaton, S. [0000-0001-7031-3510]
dc.identifier.orcidHayball, J. [0000-0002-3089-4506]
dc.identifier.orcidZannettino, A. [0000-0002-6646-6167]
dc.identifier.orcidGronthos, S. [0000-0002-6225-3084]
dc.identifier.urihttp://hdl.handle.net/2440/100245
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1023390
dc.rights© AlphaMed Press 2015
dc.source.urihttps://doi.org/10.1002/stem.2069
dc.subjectHaematopoietic stem cells; bone marrow stromal cells; EphB; ephrinB; mesenchymal stem cells
dc.titleEphB4 expressing stromal cells exhibit an enhanced capacity for hematopoietic stem cell maintenance
dc.typeJournal article
pubs.publication-statusPublished

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