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

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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.