Identification and characterization of circulating mesenchymal stem cells: novel prospects for cell-based therapy in erosive hand osteoarthritis

Erosive hand osteoarthritis (EHOA) is a severe form of osteoarthritis (OA) characterized by joint inflammation, cartilage degradation, and bone erosion. Nowadays, there have been encouraging advancements in regenerative medicine, particularly regarding the use of mesenchymal stem cells (MSCs). Key challenges involve discovering innovative and noninvasive stem cell sources and enhancing cell viability and chondrogenic potential to guarantee the efficacy of cell therapy. According to these considerations, in the first part of this study, MSCs were identified in peripheral blood and characterized in vitro to explore their regenerative potential. Chondrocytes differentiated from circulating MSCs in EHOA patients displayed elevated hypertrophic process, alteration in apoptosis and autophagy pathways, and limited chondrogenic capacity. Therefore, in the second part of the study, EHOA circulating MSCs were pretreated with resveratrol (RSV), which is known to activate SIRT1 and modulate Wnt/β-catenin signaling, promoting better survival of cells by reducing apoptosis and restoring their chondrogenic potential. Moreover, a 3D spheroid culture system was employed for a preliminary investigation, which enhanced chondrocyte development and preserved MSCs viability. Overall, these findings suggest that circulating MSCs could be a valuable and non-invasive source for regenerative medicine. Additionally, this study showed that cell preconditioning with RSV or mimicking physiological cell architecture through 3D culture techniques may enhance MSC-based therapies, offering novel treatment options for EHOA.