Skip Navigation LinksHome > December 2011 - Volume 128 - Issue 6 > Modulation of Immune Response and T-Cell Regulation by Donor...
Plastic & Reconstructive Surgery:
doi: 10.1097/PRS.0b013e318230c60b
Experimental: Original Articles

Modulation of Immune Response and T-Cell Regulation by Donor Adipose-Derived Stem Cells in a Rodent Hind-Limb Allotransplant Model

Kuo, Yur-Ren M.D., Ph.D.; Chen, Chien-Chang M.D.; Goto, Shigeru M.D., Ph.D.; Lee, I-Te M.S.; Huang, Chong-Wei M.S.; Tsai, Chia-Chun M.S.; Wang, Chun-Ting B.S.; Chen, Chao-Long M.D.

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Abstract

Background: In this study, the authors investigated whether donor adipose-derived stem cells have immunomodulatory effects, such as regulation of T cells, modulation of related cytokines, and prolongation of composite tissue allotransplantation survival, in a rodent hind-limb model.

Methods: Adipose-derived stem cells were obtained from donor adipose tissue and co-cultured with CD3+ T cells from allogenic splenocytes for in vitro studies. Orthotopic hind-limb allotransplants were performed from Brown Norway to Lewis rats (day 0). Group 1 (control group) did not receive any treatment. Group 2 received cyclosporin A on days 0 to 20. Group 3 received antilymphocyte serum (day –4 and day 1) and cyclosporin A (days 0 to 20). Group 4 received cyclosporin A (days 0 to 20), antilymphocyte serum (day –4 and day 1), and adipose-derived stem cells (2 × 106 cells/time administered intravenously on days 7, 14, and 21).

Results: Adipose-derived stem cells exert immunomodulatory effects including suppressing T-cell proliferation and increasing CD4+/CD25+/Foxp3+ regulatory T cells in vitro. The in vivo study revealed that, compared with untreated control, rats administered adipose-derived stem cells along with transient antilymphocyte serum and cyclosporin A treatment had significantly prolonged allotransplant survival (p < 0.001), decreased allotissue rejection, significantly elevated donor cell chimerism, and increased CD4+/CD25+/Foxp3+ regulatory T cells in peripheral blood and alloskin tissue with up-regulation of transforming growth factor-β and interleukin-10 levels.

Conclusions: In combination with transient immunosuppression, adipose-derived stem cells modulate the immune system and significantly prolong allotransplant survival. The underlying mechanisms include changes in antiinflammatory cytokine expression and T-cell functions.

©2011American Society of Plastic Surgeons

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