In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis

SIMPLE SUMMARY: Autologous conditioned serum (ACS) has benefits in managing osteoarthritis (OA) due to enriched mediators, including Interleukin-1 receptor antagonists (IL-1RA) and growth factors. Although ACS has become widely used in the clinic with favorable treatment outcomes in humans and animals, the study focusing on the therapeutic potential of ACS in dogs is limited. Therefore, this study investigated the therapeutic potential of ACS generated from dogs with OA, focusing on the potential anti-inflammatory and regenerative properties. We showed that ACS from OA dogs has essential mediators with immunomodulatory effects on reducing inflammation and promoting joint regeneration. We showed that ACS increased T cell suppression and FOXP3(+) T cell expansion in vitro. In addition, ACS enhanced the proliferation of joint cells and promoted chondrocyte extracellular matrix gene expression. These actions are probably caused by the mediators in ACS, including transforming growth factor, vascular endothelial growth factor, and IL-1RA. This study provides insight into the benefits of an autologous bioactive substance derived from target users as a promising potential in regenerative strategies for OA management. ABSTRACT: Osteoarthritis (OA) is mostly incurable and non-regenerative with long-term complications. Autologous conditioned serum (ACS), which is enriched in Interleukin 1 receptor antagonists (IL-1RA) and growth factors, could be an alternative treatment to accelerate the positive therapeutic effects. ACS is proposed to alleviate inflammation by blocking IL-1 receptors. However, to date, there is no report focusing on the cell-mediated anti-inflammation and regenerative effect caused by ACS, especially the ACS from patients. Therefore, this study aims to investigate the therapeutic potential of ACS generated from dogs with spontaneous OA, focusing on its promising anti-inflammatory and regenerative properties in vitro compared to the matched plasma. We found that ACS prepared from ten OA dogs contained significant concentrations of IL-1RA, vascular endothelial growth factor, and transforming growth factor beta, which are key cytokines in anti-inflammation and angiogenesis. Furthermore, we found that ACS suppressed T cell activity by reducing proliferation of effector T cells and simultaneously expanding numbers of immune suppressive FOXP3(+) T cells. Lastly, we showed that ACS enhanced the proliferation of osteocytes and fibroblasts and promoted extracellular matrix gene expression in primary chondrocyte culture. Therefore, these studies indicate that ACS prepared from dogs with OA is active as an immunomodulatory and regenerative strategy for use in OA management.