Exosomes derived from first-trimester human decidual mesenchymal stem cell

Compared with parental mesenchymal stem cells (MSCs), MSC-derived exosomes possess numerous advantages and promising application potential, including higher yield and superior bioimmunological safety. Among various MSC sources, uterine decidual tissue exhibits stronger paracrine secretion capacity and greater accessibility compared with other sources such as bone marrow. In this study, decidual tissue samples were collected from healthy women undergoing elective vaginal termination surgery at 7-11 gestational weeks. First-trimester human decidual mesenchymal stem cells (FthDMSCs) were isolated, cultured and identified via flow cytometric analysis. Subsequently, exosomes derived from FthDMSCs (FthDMSC-EXOs) were isolated and comprehensively characterized through exosomal marker protein detection, nanoparticle tracking analysis (NTA) and transmission electron microscopy. Next, a premature ovarian insufficiency (POI) mouse model was established via cyclophosphamide induction, and in vivo functional intervention was conducted using FthDMSC-EXOs. Phenotypic identification results revealed that FthDMSCs positively expressed CD105, CD73 and CD90, while barely expressed hematopoietic markers CD45, CD34 and HLA-DR. Moreover, the isolated cells possessed potent tri-lineage differentiation capacity toward osteoblasts, adipocytes and chondrocytes. Western blot results verified that exosomal markers CD9 and TSG101 were abundantly expressed in FthDMSC-EXOs. Transmission electron microscopy showed that FthDMSC-EXOs presented with typical bilayer membrane vesicle morphology. NTA demonstrated that the particle diameter of exosomes was mainly concentrated at approximately 150 nm. More importantly, in vivo experiments revealed that FthDMSC-EXOs significantly ameliorated ovarian function in POI model mice. Collectively, our study successfully isolated and characterized FthDMSC-EXOs for the first time. These findings provide a novel approach for acquiring high-quality MSC-derived exosomes and lay a solid foundation for further translational research on gynecological disease therapies.