Abstract

Mesenchymal Stromal Cells (MSCs) are multipotent cells with significant therapeutic potential in regenerative medicine, largely attributed to their immunomodulatory and differentiation capabilities. Extracellular adenosine, a critical signaling molecule, is known to regulate various MSC functions, including proliferation, migration, and differentiation into osteoblasts and adipocytes. This regulation is mediated through a family of G-protein coupled adenosine receptors (ARs: A1, A2A, A2B, and A3). While the importance of adenosine signaling is established, a comprehensive characterization of the functional expression of all AR subtypes in MSCs remains essential for understanding their precise regulatory mechanisms. In this study, we investigated the expression profile of all four AR subtypes at the mRNA level in human MSCs and employed subtype-specific agonists and antagonists to determine their functional activity. Our findings confirm the expression of all four AR subtypes in MSCs, with A2A and A2B receptors demonstrating the most prominent functional roles in modulating intracellular cAMP levels. These results provide a detailed molecular basis for the adenosinergic regulation of MSCs, which is crucial for optimizing their application in cell-based therapies and tissue engineering.