Peer-Reviewed Journal Details
Mandatory Fields
Healy, ME;Bergin, R;Mahon, BP;English, K
2015
October
Stem Cells and Development
Mesenchymal Stromal Cells Protect Against Caspase 3-Mediated Apoptosis of CD19(+) Peripheral B Cells Through Contact-Dependent Upregulation of VEGF
Published
18 ()
Optional Fields
ENDOTHELIAL GROWTH-FACTOR VERSUS-HOST-DISEASE HEMATOPOIETIC STEM-CELLS BONE-MARROW DENDRITIC CELLS IFN-GAMMA IN-VITRO T-CELL DIFFERENTIATION PROLIFERATION
24
2391
2402
The immune suppressive and anti-inflammatory capabilities of bone marrow-derived mesenchymal stromal cells (MSCs) represent an innovative new tool in regenerative medicine and immune regulation. The potent immune suppressive ability of MSC over T cells, dendritic cells, and natural killer cells has been extensively characterized, however, the effect of MSC on B cell function has not yet been clarified. In this study, the direct effect of MSC on peripheral blood B cell function is defined and the mechanism utilized by MSC in enhancing B cell survival in vitro identified. Human MSC supported the activation, proliferation, and survival of purified CD19(+) B cells through a cell contact-dependent mechanism. These effects were not mediated through B cell activating factor or notch signaling. However, cell contact between MSC and B cells resulted in increased production of vascular endothelial growth factor (VEGF) by MSC facilitating AKT phosphorylation within the B cell and inhibiting caspase 3-mediated apoptosis. Blocking studies demonstrated that this cell contact-dependent effect was not dependent on signaling through CXCR4-CXCL12 or through the epidermal growth factor receptor (EGFR). These results suggest that direct cell contact between MSC and B cells supports B cell viability and function, suggesting that MSC may not represent a suitable therapy for B cell-mediated disease.
NEW ROCHELLE
1547-3287
10.1089/scd.2015.0089
Grant Details