Establishment of a new strategy to improve graft function after lung transplantation from brain-dead donors using mesenchymal stem cells - preclinical study using MHC-inbred CLAWN miniature swine

脑死亡时的生理变化会影响器官的适宜性和移植的结果。我们首先用mhc定义的CLAWN微型猪检测供体BD是否影响早期肺功能和移植物存活。早在BD诱导后6小时，在2小时和2天的活检中观察到BD供体中促炎细胞因子的上调与炎症细胞浸润有关。此外，与非BD供体相比，使用BD供体的移植物存活时间明显缩短（26天vs 47天）。接下来，我们尝试建立猪骨髓和脂肪组织间充质干细胞（MSC），并成功培养，以建立减少脑死亡后炎症变化的新策略。在确认这些细胞为间充质干细胞的特性后，我们利用小型猪临床前肺移植模型，评估向脑死亡供者注射间充质干细胞是否有助于改善移植物功能和存活率。

Physiologic changes at brain death (BD) would affect the organ suitability and outcome of transplantation. We first examined whether donor BD affects early lung function and graft survival using MHC-defined CLAWN miniature swine. Up-regulation of proinflammatory cytokines as early as 6h after BD induction was observed in the BD donor associated with inflammatory cell infiltrates on 2-hour and 2-day biopsies. Moreover, graft survival using BD donor was significantly shorter compared to the non-BD donor (26 days vs 47 days). Next to establish a new strategy to reduce inflammatory change after brain death, we tried to establish porcine mesenchymal stem cells (MSC) derived from bone marrow and adipose tissue, and successfully cultured them. After confirmation of the characteristics of these cells as MSC, we evaluate whether injection of MSC to brain-dead donor contribute to improve graft function and survival using preclinical lung transplant model of miniature swine.