Yinmin Wang1,2, Shoubao Wang2, Chuan Gu2, Yao Xiong2, Hua Shen1, Fei Liu2, Jun Yang2. 1. Department of Plastic and Reconstructive Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. 2. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Abstract
BACKGROUND: Vascularized composite tissue allotransplantation (VCA) has increasingly been adopted for the reconstruction of tissues following severe injury. However, the side effects of the post-operative use of immunosuppressants may outweigh the benefits of VCA. In order to overcome this obstacle, ex-vivo pretreatment of allografts combined with mesenchymal stem cell-based therapy may help induce immunotolerance in composite tissue allotransplantation. METHODS: A hind-limb allotransplantation model of Brown-Norway to Lewis rats was established, and the allografts were infused with adipose-derived stem cells (ADSCs) and hypoxia primed ADSCs, which were injected through the vascular system along with short-term immunosuppressant treatment. The rejection-free survival of the allografts was monitored, and the histopathological examination of allografts was performed. The peripheral T lymphocytes and cytokines were analyzed using flow cytometry and ELISA, while Tregs infiltration in allotissue was detected using immunohistochemical staining (IHC). RESULTS: This study found that the ex-vivo treatment of allografts using ADSCs prolonged the survival of the allografts, compared with the medium control, suppressed the proliferation and infiltration of T lymphocytes and improved the secretion of immunomodulatory cytokines, such as IL-10, as well as induced regulatory T cells (Tregs) expression in the allografts. CONCLUSIONS: The ex-vivo pretreatment of allografts using ADSCs may function as an important adjunctive therapy for the induction of immunotolerance in VCA. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Vascularized composite tissue allotransplantation (VCA) has increasingly been adopted for the reconstruction of tissues following severe injury. However, the side effects of the post-operative use of immunosuppressants may outweigh the benefits of VCA. In order to overcome this obstacle, ex-vivo pretreatment of allografts combined with mesenchymal stem cell-based therapy may help induce immunotolerance in composite tissue allotransplantation. METHODS: A hind-limb allotransplantation model of Brown-Norway to Lewis rats was established, and the allografts were infused with adipose-derived stem cells (ADSCs) and hypoxia primed ADSCs, which were injected through the vascular system along with short-term immunosuppressant treatment. The rejection-free survival of the allografts was monitored, and the histopathological examination of allografts was performed. The peripheral T lymphocytes and cytokines were analyzed using flow cytometry and ELISA, while Tregs infiltration in allotissue was detected using immunohistochemical staining (IHC). RESULTS: This study found that the ex-vivo treatment of allografts using ADSCs prolonged the survival of the allografts, compared with the medium control, suppressed the proliferation and infiltration of T lymphocytes and improved the secretion of immunomodulatory cytokines, such as IL-10, as well as induced regulatory T cells (Tregs) expression in the allografts. CONCLUSIONS: The ex-vivo pretreatment of allografts using ADSCs may function as an important adjunctive therapy for the induction of immunotolerance in VCA. 2020 Annals of Translational Medicine. All rights reserved.
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