Research of inhibiting cardiac allograft rejection in mice by interleukin-35 gene modifiedmesenchyma stem cells / 中华器官移植杂志

ABSTRACT

Objective:To explore the effect and mechanism of interleukin-35 gene modified mesenchyma stem cells(MSC)on ameliorating cardiac allograft rejection and prolonging graft survival of transplanted heart in mice.Methods:In this study, IL-35-MSC secreting IL-35 continuously and steadily were successfully constructed in vitro. Abdominal heterotopic heart transplantation model was established successfully. And they were randomly divided into syngeneic control group; saline control group, MSC treatment group and IL-35-MSC experimental group(n=12 each). Six mice were randomly selected for sacrificing at Day 5 post-operation for detecting the related indicators in each group Hematoxylin eosin staining was used for pathological examination. Enzyme-linked immunosorbent assay(ELISA)was employed for detecting the concentration of IL-35 in peripheral blood and the proportion of T lymphocyte subsets in spleen was analyzed by flow cytometry(FCM). Then the remaining mice were used for recording the graft survival.Results:The model of abdominal heterotopic heart transplantation in mice was successfully constructed. As compared with saline control group(6.50±0.55 d)and MSC treatment group(12.00±0.89 days), IL-35-MSC significantly alleviated rejection after transplantation and effectively prolonged the survival time of graft(18.50±1.64 days)(n=6, P<0.01). As compared with other groups, percentage of Th17 cells and Th1/Th2 ratio in spleen decreased significantly while the proportion of CD4 + Foxp3 + Treg increased significantly in IL-35-MSC experimental group at Day 5 post-transplantation(n=6, P<0.01). Conclusions:IL-35-MSC may alleviate cardiac allograft rejection and prolong graft survival. And cellular immunotherapy based upon IL-35-MSC may provide a new approach for inducing immune tolerance.