Autophagy activation within inflammatory microenvironment improved the therapeutic effect of MSC-Derived extracellular Vesicle in SLE

作者：Shuzhen Liao, Fengbiao Guo, Zengzhi Xiao, Haiyan Xiao, Quan-ren Pan, Quan-ren Pan, Yugan Guo, Jiaxuan Chen, Xi Wang, Shuting Wang, Haimin Huang, Lawei Yang, Huafeng Liu, Qingjun Pan, Qingjun Pan · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.01.044 · 被引用次数：9 · 研究领域：Extracellular vesicles in disease、Mesenchymal stem cell research、Cardiovascular Disease and Adiposity

• SLE serum triggers the autophagic response of MSCs, while rapamycin regulates the autophagic response of MSCs induced by SLE serum. • Rapa-SLE-EV is produced by culturing MSCs with SLE serum to simulate the SLE microenvironment and activating autophagy with rapamycin. • Rapa-SLE-EV showed enhanced therapeutic potential in treating lupus mice and inhibiting B cell function. • Rapa-SLE-EV enrich more anti-inflammatory protein IDO1, and is a promising therapeutic strategy for SLE. Developing strategies to improve the therapeutic efficacy of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in autoimmune diseases have garnered increased attention. To evaluate whether rapamycin-induced autophagy within the systemic lupus erythematosus (SLE) inflammatory microenvironment (Rapa-SLE) augments the therapeutic effects of MSC-derived EVs in SLE. The therapeutic potential of the resulting EVs (Rapa-SLE-EV) was assessed in MRL/lpr mice. Rapa-SLE-EVs were compared with EVs derived from MSCs from MSCs cultured with EV-depleted fetal bovine serum (FBS-EV), EVs from MSCs cultured with rapamycin-treated FBS (Rapa-FBS-EV), and EVs exposed to SLE serum without rapamycin (SLE-EV). The autoimmune response, renal function, and pathological damage were assessed among the mouse groups. Additionally, mechanistic investigations into the role of the anti-inflammatory protein IDO1 within the EVs. Interaction with the SLE inflammatory microenvironment triggered autophagy in MSCs, which wa...