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    Mesenchymal Stromal Cells Protect Against Caspase 3-Mediated Apoptosis of CD19+ Peripheral B Cells Through Contact-Dependent Upregulation of VEGF


    Healy, Marc E. and Bergin, Ronan and Mahon, Bernard P. and English, Karen (2015) Mesenchymal Stromal Cells Protect Against Caspase 3-Mediated Apoptosis of CD19+ Peripheral B Cells Through Contact-Dependent Upregulation of VEGF. Stem Cells and Development, 24. pp. 2391-2402. ISSN 1547-3287

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    Abstract

    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 contactdependent 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.

    Item Type: Article
    Keywords: Mesenchymal Stromal Cells; Caspase 3-Mediated Apoptosis; CD19+ Peripheral B Cells; Contact-Dependent Upregulation; VEGF;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10581
    Identification Number: https://doi.org/10.1089/scd.2015.0089
    Depositing User: Karen English
    Date Deposited: 25 Feb 2019 14:27
    Journal or Publication Title: Stem Cells and Development
    Publisher: Mary Ann Liebert
    Refereed: Yes
    URI:

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