2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644625摘要：因腦死生理變化會對肺臟造成相當程度的傷害，導致８５％以上腦死捐贈肺器官無法達到可供移植的捐贈標準，若能減少腦死過程所引發之生理免疫反應對肺組織所造成的傷害，則能有效提高捐贈肺器官之可利用率。我們已經建立一套無血清培養系統，能夠自人類胎盤的絨毛膜蛻膜層中分離出間葉幹細胞，而此間葉幹細胞已在in vitro與in vivo的實驗中證明具有抑制免疫反應並延緩發炎的療效。因此本計畫欲探討間葉幹細胞對腦死過程所造成之急性肺損傷的修復能力，以增加肺器官的使用率。我們將以豬隻為動物實驗模式，分為三個階段進行探討。首先，我們將測試由靜脈給予之間葉幹細胞對於正常豬隻肺部組織所造成的相關臨床反應，並以本團隊所研發之螢光奈米鑽石(FND@HSA)細胞標的技術，追蹤間葉幹細胞在肺組織的反應部位。第二階段則利用我們已建立之體外肺灌流系統(Ex Vivo Lung Perfusion)，以豬隻腦死後器官捐贈模式，來驗證間葉幹細胞修復急性肺損傷之能力，同時分析相關的訊號傳遞機轉。第三階段則將經間葉幹細胞修復後之腦死捐贈肺器官，進行豬隻單肺移植手術，以實際模擬臨床治療模式來觀察間葉幹細胞之長期修復療效。希冀透過此動物實驗之結果，能大幅增加邊緣性器官的使用率，為等待肺臟移植之病患提供更多的捐贈器官。<br> Abstract: Physiological changes after brain death would cause considerable damage to the lungs, leading more than 85% of brain-dead donor lungs unavailable to meet the transplant criteria. If the lung injury due to the physiological process of immune response triggered by the brain death is reduced, the availability of donor lungs can be effectively increased. We have established a serum-free culture system, which is able to isolate mesenchymal stem cells from human placental chorionic decidua layer. Both in vitro and vivo experiments, the placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) has been proven to significantly suppress the immune response and delay the progression of disease. In order to increase the utilization of marginal lung donor clinically, therefore, this project will discuss the effect of pcMSCs treatment on acute lung injury from pig brain-dead donation model. This projected will proceed through three study stages. At the first stage, we will test the clinical response of the pcMSCs in the normal pig, and use the fluorescence nanodiamond (FND @ HSA) as a tracer to trace the localization of the pcMSCs after they were injected into the pig. At the same time, we will also analyze the safety of the pcMSCs treatment. During the second stage, we will validate the repair ability of pcMSCs on the acute lung injury from the brain-dead donation model. We will also use the ex vivo lung perfusion system (EVLP) to test the short-term treatment effect of pcMSCs on acute lung injury, which was triggered during the brain-dead course. The related signal pathways will also be tested during this stage. Finally, we will use the pig lung transplantation model to test the clinical utility of pcMSCs treatment. The pcMSCs treated lung donor will be harvested from a brain-dead pig, ex vivo cultured in the EVLP for 4 hours, and then transplanted into another pig. Hope the results of our project could provide useful information for the utilization of pcMSCs treatment in the marginal lung donors from brain-death donation.