骨髓间充质干细胞生物反应器的构建及对脓毒症大鼠免疫失衡的双向调控作用

项目名称： 骨髓间充质干细胞生物反应器的构建及对脓毒症大鼠免疫失衡的双向调控作用

项目编号： No.81470990

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 丁峰

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 脓毒症是严重威胁人类健康的常见病，其发病关键的病理生理机制是免疫失衡。骨髓间充质干细胞(bMSCs)具有强大的抗炎特性和免疫调节作用，已在脓毒症的治疗中取得一定的效果。申请者尝试构建MSCs生物反应器，既保留了其免疫调节作用，又发挥生物反应器的免疫隔绝作用，避免异体干细胞输注可能带来的生物安全问题。申请者构建了大鼠盲肠结扎加穿孔(CLP)模型和慢性肾脏病(5/6肾大切)合并CLP二次打击模型，分别模拟脓毒症免疫激活(SIRS)和免疫抑制(CARS)状态。初步结果显示，bMSCs生物反应器可根据动物的免疫状况发挥双向免疫调控作用。申请者拟进一步完善MSCs生物反应器，探索干细胞生物反应器治疗脓毒症的效果及可能机制，尤其是探讨对脓毒症不同免疫状态的双向免疫调控作用。本课题研究结果将为临床上脓毒症的治疗提供一种全新的安全、有效的治疗手段。

中文关键词： 生物反应器；脓毒症；骨髓间充质干细胞；免疫调节

英文摘要： Sepsis is a common disease that severely threatens the people's health. Increasing evidence supports a central role for immunosuppression in sepsis. Bone marrow mesenchymal stem cells (bMSCs) possess a strong ability to ameliorate inflammation and restore immune system. It has been proved that bMSCs have beneficial effects in the experimental sepsis. Our group has constructed a bMSCs bioreactor which maintains the nature of immune regulation and possesses the feature of immune isolation, avoiding the safety issue of allogenic cell transplantation. We underwent a sepsis model of cecal ligation and puncture (CLP) and a two-hit model of chronic kidney disease (5/6 nephrectomy) followed by CLP to mimic SIRS and CARS separately. Our pilot study demonstrated that the bMSCs bioreactor has the ability of bilateral immune regulation according to the state of experimental sepsis. We intend to improve the bMSCs bioreactor, investigate its potential effects and mechanisms, especially the benefit effects on bilateral immune regulation in sepsis. We believe this research will provide a brand-new, safe and effective approach in the management of sepsis.

英文关键词： bioreactor;sepsis;bone marrow mesenchymal stem cells;immunomodulation