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.
Conclusions
The ex-vivo pretreatment of allografts using ADSCs may function as an important adjunctive therapy for the induction of immunotolerance in VCA.
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.