E-Poster Presentation 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

Background: Osteoarthritis is a leading cause of chronic pain and disability, for which there is no cure. Mesenchymal stem cells (MSCs) have recently brought new hope for treating osteoarthritis due to their ability to send anti-inflammatory and trophic signals to surrounding tissues. Interestingly, the few available clinical trials utilising MSCs to treat knee osteoarthritis have not demonstrated consistent benefits.

Aim:  This study aims to unravel the mechanisms behind the variable efficacy of stem cell injections for osteoarthritis using an in vitro model of a human osteoarthritic joint.

Methods: MSCs were co-cultured with human synovial fibroblasts (HSFs) isolated from osteoarthritic joint tissues, for up to 21 days in growth, osteogenic and chondrogenic media (simulating the relevant conditions in a joint environment). Cell interactions were assessed using RT-PCR (n=4) and histology (n=2).

Results: MSCs co-cultured with osteoarthritic HSFs showed increased inflammation (MMP2, ADAMTS5 upregulation) and impaired ability to form new bone (reduced BSP, SPP1 expression and calcium deposition) and cartilage (reduced COL2A1, ACAN expression and proteoglycan deposition) at 21 days, suggesting that the osteoarthritic joint is a highly inhibitory environment that negatively influences MSCs and reduces their therapeutic effects. Furthermore, short-term (3 days) exposure of the osteoarthritic HSFs to MSCs ('pre-conditioning') was insufficient for sustained modifications to their diseased phenotype. The osteoarthritic HSFs, whether previously exposed to MSCs or not, had similar expression profiles of inflammatory markers, and also had similar negative effects on MSCs, including inflammatory marker upregulation e.g. IL-8, ADAMTS4 and impaired chondrogenesis.

Conclusion: Diseased cells in an osteoarthritic joint create an inflammatory environment that impairs healing. Although MSCs have anti-inflammatory and trophic functions, they may develop a diseased phenotype similar to osteoarthritic cells following injection and show reduced therapeutic effects. Future regenerative therapies for osteoarthritis may have greater success by focusing on the biological derivatives of stem cells.