<b>Amniotic Epithelial Cell Microvesicles Uptake Inhibits PBMCs and Jurkat Cells Activation by Inducing Mitochondria-Dependent Apoptosis</b>

Amniotic epithelial cells (AEC) exhibit significant immunomodulatory and pro-regenerative properties, largely due to their intrinsic paracrine functions, which are currently harnessed through the collection of their secretomes. While there is increasing evidence of the role of bioactive components freely secreted or carried by exosomes, the bioactive cargo of AEC microvesicles (MV) and their crosstalk with the immune cells remains to be fully explored. We showed that under intrinsic conditions or in response to LPS, AEC-derived MV carries components such as lipid-mediated signaling molecules, ER, and mitochondria. They foster the intra/interspecific mitochondrial transfer into immune cells (PBMCs and Jurkat cells) <i>in vitro</i> and <i>in vivo</i> on the zebrafish larvae model of injury. The internalization of MV cargoes through macropinocytosis induces hyperpolarization of PBMC mitochondrial membranes and triggers MV-mediated apoptosis. This powerful immune suppressive mechanism triggered by AEC-MV cargo delivery paves the way for controlled and targeted cell-free therapeutic approaches.羊膜上皮细胞（Amniotic epithelial cells, AEC）具备显著的免疫调节与促再生特性，这主要源于其固有的旁分泌功能，目前学界已通过收集其分泌组（secretomes）对该功能进行开发利用。尽管已有越来越多研究证实，外泌体（exosomes）自由分泌或携带的生物活性成分发挥着关键作用，但羊膜上皮细胞微囊泡（microvesicles, MV）的生物活性载荷及其与免疫细胞的串扰机制，仍有待全面阐明。本研究证实，在固有状态或脂多糖（LPS）刺激下，羊膜上皮细胞来源的微囊泡可携带脂质介导的信号分子、内质网（Endoplasmic Reticulum, ER）及线粒体等组分。这类微囊泡可在体外（in vitro）及以斑马鱼幼虫损伤模型开展的体内（in vivo）实验中，促进线粒体在种内与种间向免疫细胞（外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMCs）与Jurkat细胞）的转移。通过巨胞饮作用（macropinocytosis）内化微囊泡载荷物，可诱导外周血单个核细胞的线粒体膜超极化，并触发微囊泡介导的细胞凋亡。这种由羊膜上皮细胞微囊泡载荷递送所介导的强效免疫抑制机制，为可控且靶向的无细胞治疗方案开辟了全新路径。