Administration of adipose stromal vascular fraction attenuates acute rejection in donation after circulatory death rat renal transplantation.

Abstract

Stem cell therapy represents a new approach to induce immune tolerance in solid organ transplantation. However, the time-consuming process of stem cell expending limits the range of stem cell treatment. Uncultured adipose stromal vascular fraction is considered an attractive cell source for cell-based therapy. This study aimed to evaluate the effect of stromal vascular fraction on the immune system in donation after circulatory death rat renal transplantation. Stromal vascular fraction cells and splenocytes were co-cultured to evaluate the effect of stromal vascular fraction on splenocyte proliferation and viability. Sprague-Dawley rats were used as donors. and Wistar rats as recipients to establish a donation after a circulatory death rat renal transplantation model. Warm ischemia time was 5min. Stromal vascular fraction was administered in the rat model following the intra-arterial route. The spleens and grafts of recipients were harvested on days1, 3 and 7 post-transplantation for assessing acute rejection, infiltration of inflammatory cells, indoleamine 2, 3-dioxygenase expression and T-cell frequency in the spleen. Stromal vascular fraction could inhibit proliferation and induce apoptosis of splenocytes invitro (P<0.05). The administration of stromal vascular fraction could significantly reduce acute rejection and infiltration of CD8+ Tcells and mononuclear macrophages in grafts, and increase indoleamine 2, 3-dioxygenase expression (P<0.05). The frequency of CD8+ Tcells decreased, and the frequency of CD25+ Foxp3+ regulatory Tcells increased in the spleen of the acute rejection+stromal vascular fraction group on day 7 post-transplantation (P<0.05). Administration of the adipose stromal vascular fraction could attenuate acute rejection in donation after circulatory death renal transplantation by increasing the ratio of regulatory Tcells and enhancing indoleamine 2, 3-dioxygenase expression.