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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.

Plastic and Reconstructive Surgery: December 2011 - Volume 128 - Issue 6 - p 661e–672e
doi: 10.1097/PRS.0b013e318230c60b
Experimental: Original Articles
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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.

Kaohsiung, Taiwan

From the Department of Plastic and Reconstructive Surgery, Medical Research, and the Liver Transplantation Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine.

Received for publication March 12, 2011; accepted June 10, 2010.

Disclosure:The authors have no financial interest o declare in relation to the content of this article.

Yur-Ren Kuo, M.D., Ph.D.; Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 83305, Taiwan, t1207816@ms22.hinet.net

©2011American Society of Plastic Surgeons