A Single Administration of Synthetic Artificial Stem Cells (SASC) Attenuates Osteoarthritis Progression

PurposeOsteoarthritis (OA) is a highly prevalent joint disease for which common therapies may provide symptomatic relief but have failed to provide a curative solution. There has been a growing interest in disease-modifying therapies, such as the use of stem cells and bioactive factors in treating OA. The synthetic artificial stem cell (SASC) system has previously been introduced as one such disease-modifying therapy: designed to mimic the paracrine effect of biological stem cells but with the added ability to engineer the composition and tailor it to different tissue types.MethodsIn the present study, the efficacy of a single intra-articular injection was evaluated across three doses (1, 3, or 5 million) of SASC cells in a collagenase-induced OA rat model. Inflammation was monitored by joint swelling through the 63 day treatment period and structural and functional cartilage regeneration outcomes as well as local immune and inflammatory outcomes were evaluated by histology, nano-indentation of the gross cartilage, and immunohistochemistry. Further, in vitro SASC modulation of the NF-kappa beta pathway was observed by monitoring various upstream and downstream gene expression profiles along the pathway.ResultsA single administration of 3 million and 5 million SASC cells reduced knee swelling attenuates cartilage degeneration as observed by Safranin O staining, compared to the OA control. Further, major genes along the NF-kappa beta pathway were significantly modulated by SASC to a similar extent compared to ADSC control.ConclusionThe present study demonstrated that SASC Cells have a dose-dependent response in attenuating collagenase-induced OA progression and effectively modulates the major inflammatory pathway involved in the pathogenesis of OA.Lay SummaryIn this study, we investigated the efficacy of synthetic artificial stem cells (SASC) in treating osteoarthritis (OA). Different doses of SASC cells were injected into rats with OA. Higher doses of SASC cells reduced knee swelling, protected against cartilage degeneration, and modulated the inflammatory NF-kappa beta pathway. This work highlights potential of SASC cells as a curative treatment for OA.