Xu Fang, Fei Ziying, Dai Huaxing, Xu Jialu, Fan Qin, Shen Shufang, Zhang Yue, Ma Qingle, Chu Jiacheng, Peng Fei, Zhou Fangfang, Liu Zhuang, Wang Chao
Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, China.
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02114, USA.
Adv Mater. 2022 Jan;34(1):e2106265. doi: 10.1002/adma.202106265. Epub 2021 Oct 23.
Autoimmune diseases are the third most common disease influencing the quality of life of many patients. Here, a programmed cell death-ligand 1 + (PD-L1) mesenchymal stem cell (MSC) derived extracellular vesicles (MSC-sEVs-PD-L1) using lentivirus-mediated gene transfection technology is developed for reconfiguration of the local immune microenvironment of affected tissue in autoimmune diseases. MSC-sEVs-PD-L1 exhibits an impressive ability to regulate various activated immune cells to an immunosuppressed state in vitro. More importantly, in dextran sulfate sodium-induced ulcerative colitis (UC) and imiquimod-induced psoriasis mouse models, a significantly high accumulation of MSC-sEVs-PD-L1 is observed in the inflamed tissues compared to the PD-L1+ MSCs. Therapeutic efficiency in both UC and psoriasis mouse disease models is demonstrated using MSC-sEVs-PD-L1 to reshape the inflammatory ecosystem in the local immune context. A technology is developed using MSC-sEVs-PD-L1 as a natural delivery platform for autoimmune diseases treatment with high clinical potential.
自身免疫性疾病是影响许多患者生活质量的第三大常见疾病。在此，利用慢病毒介导的基因转染技术开发了一种程序性细胞死亡配体1阳性（PD-L1）间充质干细胞（MSC）衍生的细胞外囊泡（MSC-sEVs-PD-L1），用于重塑自身免疫性疾病中受影响组织的局部免疫微环境。MSC-sEVs-PD-L1在体外具有将各种活化免疫细胞调节至免疫抑制状态的惊人能力。更重要的是，在葡聚糖硫酸钠诱导的溃疡性结肠炎（UC）和咪喹莫特诱导的银屑病小鼠模型中，与PD-L1阳性的间充质干细胞相比，在炎症组织中观察到MSC-sEVs-PD-L1有显著更高的聚集。使用MSC-sEVs-PD-L1在局部免疫环境中重塑炎症生态系统，证明了其在UC和银屑病小鼠疾病模型中的治疗效果。开发了一种以MSC-sEVs-PD-L1作为天然递送平台治疗自身免疫性疾病的技术，具有很高的临床潜力。
