Adipose-derived stromal cells modulating composite allotransplant survival is correlated with B cell regulation in a rod
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RESEARCH
Open Access
Adipose-derived stromal cells modulating composite allotransplant survival is correlated with B cell regulation in a rodent hind-limb allotransplantation model Chien-Chang Chen1,2†, Rong-Fu Chen1†, Jheng-Syuan Shao1, Yun-Ting Li1, Yu-Chi Wang1, Gerald Brandacher3, Jiin-Haur Chuang4 and Yur-Ren Kuo1,5,6,7*
Abstract Background: Our previous studies demonstrated that adipose-derived mesenchymal stromal cells (ASCs) have immunomodulatory effects that prolong allograft survival in a rodent hind-limb allotransplant model. In this study, we investigated whether the effects of immunomodulation by ASCs on allograft survival are correlated with B cell regulation. Methods: B cells isolated from splenocytes were cocultured with ASCs harvested from adipose tissue from rodent groin areas for in vitro experiments. In an in vivo study, hind-limb allotransplantation from Brown-Norway to Lewis rats was performed, and rats were treated with ASCs combined with short-term treatment with anti-lymphocyte serum (ALS)/cyclosporine (CsA) as immunosuppressants. Peripheral blood and transplanted tissue were collected for further analysis. Result: An in vitro study revealed that ASCs significantly suppressed lipopolysaccharide-activated B cell proliferation and increased the percentage of Bregs. The levels of immunoregulatory cytokines, such as TGF-β1 and IL-10, were significantly increased in supernatants of stimulated B cells cocultured with ASCs. The in vivo study showed that treatment with ASCs combined with short-term ALS/CsA significantly reduced the B cell population in alloskin tissue, increased the proportion of circulating CD45Ra+/Foxp3+ B cells, and decreased C4d expression in alloskin. Conclusion: ASCs combined with short-term immunosuppressant treatment prolong allograft survival and are correlated with B cell regulation, C4d expression and the modulation of immunoregulatory cytokines. Keywords: Adipose-derived stromal cells, Regulatory B cell, Vascularized composite allotransplantation
* Correspondence: [email protected] † Chien-Chang Chen and Rong-Fu Chen have equal contribution as co-first author. 1 Division of Plastic & Reconstructive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 100 Tzyou 1st Rd., Kaohsiung 80756, Taiwan 5 Faculty of Medicine, College of Medicine, Orthopaedic Research Center, Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise
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