脂肪组织间充质干细胞来源的微囊泡对细菌性肺炎引起的败血症保护作用机制研究

Sepsis, mainly induced by bacterial pneumonia, is a serious clinical condition. Now the clinical research of sepsis has gone from failure to failure, there is an urgent need for new therapy. Mesenchymal stem cells (MSCs) is a group of heterogeneous cells, and exert self-renewal and multilineage differentiation potential. MSCs can inhibit tissue injury, regulate immune response and promote cell self-repair via paracrine mechanism. MSCs secret soluble factors and microvesicles. Microvesicles carrying mRNA or microRNA from parent cells could induce epigenetic reprogramming of target cells, which is believed to be the major route of mesenchymal stem cell derived microvesicles(MSC-MV)-involved repair. Based on previous studies, we will first isolate and purify MSC-MV from adipose tissue, compare the effect of MSCs and MSC-MV on the phagocytic, bactericidal and reactive oxygen species production of alveolar macrophages in vitro, and investigate soluble factors mRNA profile of MSC-MV. The effect of MSCs and MSC-MV in vivo will be investigated in murine model of bacterial pneumonia induced sepsis. The major observation items include mortality, parameters of lung inflammatory and lung injury. MSCs and MSC-MV are expected to play a role of anti-inflammatory, anti-infection and regulating immune response, and involved in the repair of inflammatory lung injury. This study is expected to provide a potential new way for the intervention of life-threatening bacterial pneumonia induced sepsis.

临床上急需新的治疗策略来应对细菌性肺炎引起的败血症带来的挑战。间充质干细胞(MSCs)具有自我更新能力和向多系细胞分化的潜能，可通过旁分泌机制抑制组织损伤、调节免疫反应和促进细胞自我修复。MSCs微囊泡（MSC-MV）可将MSCs的遗传信息传递到靶细胞中，使其具有新的遗传特征。基于上述设想本研究将首先分离脂肪组织来源MSCs并提取MSC-MV，然后比较MSCs和MSC-MV对巨噬细胞功能的影响，探索MSC-MV携带可溶性抗炎因子mRNA表达模式。随后经静脉回输MSCs和MSC-MV至细菌性肺炎败血症小鼠模型，进一步将通过检测死亡率、肺部炎症反应和肺损伤等项目来比较两者对败血症的干预疗效和具体机制。研究预期MSCs和MSC-MV在体内发挥抗炎、抗感染作用、调节免疫作用，同时修复肺损伤。研究预期为细菌性肺炎引起的败血症治疗提供一条潜在新途径。