Understanding the effects of mesenchymal stromal cell therapy for treating osteoarthritis using an in vitro co-culture model

Abstract: Osteoarthritis (OA) is a leading cause of chronic pain and disability, for which there is no cure. Mesenchymal stromal cells (MSCs) have been used in clinical trials for treating OA due to their unique functions to send paracrine anti-inflammatory and trophic signals. Interestingly, these studies have shown mainly short-term effects of MSCs in improving pain and joint function, rather than sustained and consistent benefits. This may reflect a change or loss in the therapeutic effects of MSCs after intra-articular injection. This study aimed to unravel the reasons behind the variable efficacy of MSC injections for OA using an in vitro co-culture model. Osteoarthritic human synovial fibroblasts (OA-HSFs) exposed to MSCs showed short-term downregulation of pro-inflammatory and pro-catabolic genes, but the MSCs showed upregulation of pro-inflammatory genes and impaired ability to undergo osteogenesis and chondrogenesis in the presence of OA-HSFs. Moreover, short-term exposure of OA-HSFs to MSCs was insufficient for inducing sustained changes to their diseased behaviour. These findings suggest MSCs may not provide long-term effects in correcting the OA joint environment due to adopting the diseased phenotype of the surrounding tissues, which have important implications in the future development of effective stem cell-based OA treatments with long-term therapeutic efficacy.