糖蛋白修饰间充质干细胞在脂肪供肝肝移植缺血再灌注损伤中的保护作用及机制研究

Safe use of fat donor liver is an effective means to alleviate the shortage of donor liver. However, fat donor liver is sensitive to ischemia-reperfusion injury and may lead to postoperative primary non-function, early graft dysfunction, delayed graft recovery and ischemia Sexual biliary lesions and so on. Studies have shown that mesenchymal stem cells have the potential of regeneration and differentiation, can promote liver cell regeneration, but because of its inability to effectively target the ischemic liver tissue distribution, the treatment effect is limited. While selectin is one of the markers of ischemia-reperfusion injury in fatty liver, it accumulates in the tissue or cells of ischemia-reperfusion injury, and glycoprotein-modified mesenchymal stem cells can specifically bind with selectin. Therefore, we put forward strategies to improve MSCs accurate retention in liver ischemia-reperfusion injury and promote hepatocyte regeneration and tissue repair: (1) Preparation of stable glycoprotein modified mesenchymal stem cells 19Fc-PPG-MSCs; (2) In vitro experiments to explore its adhesion function in the repair of ischemia-reperfusion injury of fat donor liver transplantation for selectin and confirm its biological stability; (3) in vivo experiments to verify the 19Fc-PPG-MSCs Repair of ischemia-reperfusion injury in fatty liver during liver transplantation and explore specific mechanisms. To provide a theoretical basis and new ideas for improving the precise and effective treatment of ischemia-reperfusion injury of fat donor liver graft by stem cells.

安全使用脂肪供肝是缓解供肝短缺的有效手段，但脂肪肝对缺血再灌注损伤异常敏感，导致术后原发性无功能、早期移植物功能不良等。研究表明间充质干细胞具有再生及分化潜能，可以促进移植肝细胞再生，但由于其不能在肝组织中有效定向分布，治疗效果有限。选择素是脂肪肝缺血再灌注损伤的标志物之一，聚集在缺血再灌注损伤的组织或细胞中，而糖蛋白修饰的间充质干细胞可以与选择素特异性结合。故此我们提出了提高间充质干细胞在肝缺血再灌注损伤部位精确停留、促进肝细胞再生和组织修复的策略（1）制备稳定的糖蛋白修饰的间充质干细胞19Fc-PPG-MSCs（2）在体外实验中探究其在修复脂肪供肝肝移植缺血再灌注损伤中对选择素的黏附功能改变情况，并证实其生物稳定性（3）体内实验验证19Fc-PPG-MSCs对脂肪肝肝移植缺血再灌注损伤的修复作用并探索具体机制。为提高干细胞精确有效治疗脂肪供肝肝移植后缺血再灌注损伤提供理论依据和新思路。

安全使用脂肪供肝是缓解供肝短缺的有效手段，但脂肪肝对缺血再灌注损伤异常敏感，导致术后原发性无功能、早期移植物功能不良等。研究表明间充质干细胞具有再生及分化潜能，可以促进移植肝细胞再生，但由于其不能在肝组织中有效定向分布，治疗效果有限。选择素是脂肪肝缺血再灌注损伤的标志物之一，聚集在缺血再灌注损伤的组织或细胞中，而糖蛋白修饰的间充质干细胞可以与选择素特异性结合。故此我们提出了提高间充质干细胞在肝缺血再灌注损伤部位精确停留、促进肝细胞再生和组织修复的策略（1）制备稳定的糖蛋白修饰的间充质干细胞19Fc-PPG-MSCs（2）在体外实验中探究其在修复脂肪供肝肝移植缺血再灌注损伤中对选择素的黏附功能改变情况，并证实其生物稳定性（3）体内实验验证19Fc-PPG-MSCs对脂肪肝肝移植缺血再灌注损伤的修复作用并探索具体机制。为提高干细胞精确有效治疗脂肪供肝肝移植后缺血再灌注损伤提供理论依据和新思路。