182. Effects of Inflammation-Mediated Autophagy of Human Placental Mesenchymal Stem Cells of Fetal Origin on Their Immunomodulatory Properties and Therapeutic Potential in Bleomycin-Induced Pulmonary Fibrosis Models

Pulmonary fibrosis (PF) is an interstitial pulmonary disease caused by lung injury and inflammatory response, which is currently incurable in clinical settings. Fibroblast proliferation and extracellular matrix accumulation are the main clinical manifestation and pathogenic features of PF. An compelling number of evidence has demonstrated that mesenchymal stem cells (MSCs) pose therapeutic potentials in PF disease, owing to their strongly immunomodulatory roles in injury repair of tissues, including the lung. In this regards, the autophagy of MSCs induced by inflammatory microenvironment of pulmonary injury plays a critical role in their immunomodulatory properties. Our works have recently revealed that human placental MSCs of fetal origin (fPMSCs) have an ability to alleviate and reverse the pathological progress in a bleomycin-induced PF model. In order to better understand mechanisms underpinning the therapeutic effect of fPMSCs in pulmonary fibrosis, the inflammation-mediated MSC autophagy in murine pulmonary fibrosis model was interrogated. Our results demonstrated that the inflammatory microenvironment of PF was able to induce MSC autophagy in vitro and in vivo, implying that the inflammatory microenvironment of PF may trigger autophagy of fPMSCs, which in turn affects their therapeutic potentials to PF. These results also suggest that an interaction between autophagy of fPMSCs and PF inflammatory microenvironment may have a fundamental impact on immunomodulatory functions and therapeutic effects of fPMSCs on pulmonary. Key words: placenta; mesenchymal stem cells; cell therapy; pulmonary fibrosis; autophagy.