Kidney-Derived Mesenchymal Stromal Cells Modulate Dendritic Cell Function to Suppress Alloimmune Responses and Delay Allograft Rejection
- Authors
- Huang, Yanfei; Chen, Ping; Zhang, Cassie B.; Ko, Gang Jee; Ruiz, Miriam; Fiorina, Paolo; Hussain, Mehboob A.; Wasowska, Barbara A.; Rabb, Hamid; Womer, Karl L.
- Issue Date
- 27-12월-2010
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- Dendritic cells; Antigen-presenting cells; Islet transplantation; Mesenchymal stem cells
- Citation
- TRANSPLANTATION, v.90, no.12, pp.1307 - 1311
- Indexed
- SCIE
SCOPUS
- Journal Title
- TRANSPLANTATION
- Volume
- 90
- Number
- 12
- Start Page
- 1307
- End Page
- 1311
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/115095
- DOI
- 10.1097/TP.0b013e3181fdd9eb
- ISSN
- 0041-1337
- 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.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
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