EphB4 Expressing Stromal Cells Exhibit an Enhanced Capacity for Hematopoietic Stem Cell Maintenance
| Autor: | Louise E. Purton, Sharon Paton, Romana Panagopoulos, Koichi Matsuo, John D. Hayball, Andrew C.W. Zannettino, Thao Nguyen, Agnieszka Arthur, Stan Gronthos |
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| Přispěvatelé: | Nguyen, Thao M, Arthur, Agnieszka, Panagopoulos, Romana, Paton, Sharon, Hayball, John D, Zannettino, Andrew CW, Purton, Louise E, Matsuo, Koichi, Gronthos, Stan |
| Rok vydání: | 2014 |
| Předmět: |
Stromal cell
Molecular Sequence Data Receptor EphB4 CD34 Stem cell factor Mice Transgenic ephrinB Biology Mice medicine Lymph node stromal cell Animals Humans Amino Acid Sequence EphB Cells Cultured mesenchymal stem cells adult haematopoietic stem cells Hematopoietic stem cell Cell Biology marrow stromal stem cells Hematopoietic Stem Cells Cell biology medicine.anatomical_structure Gene Expression Regulation Immunology Molecular Medicine Stem cell Stromal Cells Developmental Biology Homing (hematopoietic) Adult stem cell bone marrow stromal cells |
| Zdroj: | Stem cells (Dayton, Ohio). 33(9) |
| ISSN: | 1549-4918 |
| Popis: | 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. Stem Cells 2015;33:2838—2849 |
| Databáze: | OpenAIRE |
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