Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection

Yanfei Huang, Ping Chen, Cassie B. Zhang, Gang Jee Ko, Miriam Ruiz, Paolo Fiorina, Mehboob A. Hussain, Barbara A. Wasowska, Hamid Rabb, Karl L. Womer

    Research output: Contribution to journalArticlepeer-review

    23 Citations (Scopus)

    Abstract

    Background. Mesenchymal stromal cells (MSCs) are multipotent cells with immunoregulatory capacity that are present in most adult organs. We previously demonstrated that co-culture of C57BL/6 kidney-derived MSCs (KSCs) in syngeneic bone marrow-derived dendritic cell (DC) culture induced a DC phenotype (KSC-DC) with reduced major histocompatibility complex (MHC) class II/increased CD80 expression and ability to suppress T-cell responses. Methods. To study their effects on allogeneic DCs, C57BL/6 KSCs were added to incipient BALB/c DC culture, with surface expression of MHC class II/CD80 measured by fluorescence-activated cell sorting. The ability to stimulate T-cell responses was then assessed in an allogeneic mixed leukocyte response. Next, we isolated either BALB/c (donor) or C57BL/6 (recipient) KSC-DCs from co-culture and measured the tempo of rejection after cotransplantation with islet grafts in a mouse model of islet transplantation. Finally, we measured the effects of KSC-DC stimulation on B-cell proliferation and IgM/IgG production in allogeneic cultures. Results. C57BL/6 KSCs induced a BALB/c DC phenotype with significantly decreased MHC class II, increased CD80 expression, and decreased T-cell stimulatory capacity in the mixed leukocyte response (P<0.01 vs. control). Cotransplantation of donor (BALB/c) but not recipient (C57BL/6) KSC-DCs resulted in significant delay of rejection after islet transplantation (P<0.01 vs. control). Finally, stimulation by KSC-DCs resulted in significantly reduced B-cell proliferation and antibody production in allogeneic culture (P<0.01 vs. control). Conclusions. Our results highlight an important mechanism of MSC-based immunotherapy and its potential for use in clinical transplantation as prevention of rejection and possibly sensitization.

    Original languageEnglish
    Pages (from-to)1307-1311
    Number of pages5
    JournalTransplantation
    Volume90
    Issue number12
    DOIs
    Publication statusPublished - 2010 Dec 27

    Keywords

    • Antigen-presenting cells
    • Dendritic cells
    • Islet transplantation
    • Mesenchymal stem cells

    ASJC Scopus subject areas

    • Transplantation

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