期刊
TRANSPLANTATION
卷 90, 期 12, 页码 1307-1311出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181fdd9eb
关键词
Dendritic cells; Antigen-presenting cells; Islet transplantation; Mesenchymal stem cells
资金
- National Kidney Foundation of Maryland
- Juvenile Diabetes Research Foundation
- NIH [RO1 81472, R01DK054770]
- Baltimore Diabetes Research and Training Center (NIH) [P6O 79637]
- American Heart Association
- Roche Organ Transplantation Research Foundation (ROTRF) [513443778]
- Talecris Biotherapeutics, Inc.
- Talent Program
- NIDDK [K08DK66319]
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.
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