Biological characteristics of menstrual blood-derived endometrial stem cell-derived secretome and its therapeutic potential

This study aims to systematically characterize the protein and metabolite compositions of the secretome isolated from menstrual blood-derived endometrial stem cell (MenSC-S), elucidate its biological properties, explore potential active components and mechanisms of action as an acellular therapeutic agent, and provide a scientific foundation for advancing its clinical applications. A total of 878 shared proteins were identified in MenSC-S samples from volunteers of varying ages (25, 35, and 45 years), among which 242 were recognized as secretory proteins. The investigation revealed that the key protein heat shock protein family A member 8 (HSPA8) negatively regulates the assembly of the NLRP3 inflammasome complex by activating the PI3K-Akt signaling pathway. Untargeted metabolomic analysis indicated that metabolites present in MenSC-S play significant roles in biological processes such as nitrogen metabolism, amino acid synthesis, and detoxification. Integrated protein-metabolite analysis highlighted the considerable complexity of both proteome and metabolome along with their synergistic effects. Dialysis experiments confirmed that the metabolite fractions within MenSC-S are crucial for enhancing cell viability in both normal cells and those damaged by Cisplatin. This study partially elucidates the biological properties of MenSC-S along with potential molecular mechanisms underlying its therapeutic effects. It not only identifies specific potential active components for developing acellular therapeutic strategies targeting various diseases based on MenSC-S but also establishes a foundation for further exploration into the clinical translation of mesenchymal stem cells (MSCs) and their derivatives.