Stem cell modelling of osteoarthritis using an organ-on-a-chip approach.

Osteoarthritis (OA) is a chronic degenerative joint disease that affects more than 200 million people globally. Despite its high prevalence, treatment efficacy remains low, largely due to the complex nature of the disease and the significant variability in response to medication of individual patients. Both genetic and environmental factors play a major role in disease progression and in how patients respond to various therapies, making personalised treatment strategies crucial for effective disease management. In light of these challenges, there is an urgent need for reliable, objective tools that can assess the response of individual patients to different medications. This would allow clinicians to tailor treatments based on a patient's unique genetic and biological profile, improving outcomes and minimizing unnecessary side effects. Here we are presenting a method, where we are differentiating mesenchymal stem cells (MSCs) into the chondrogenic lineage using a 3D organ-on-a-chip approach. Two sources of MSCs, the infrapatellar fat pad and abdominal adipose tissue are compared using targeted gene expression analysis and morphological assessment. In addition, we assessed how gene expression is changed after artificially inflammatory exposure with medications compared to that in untreated cells. We found that both abdominal adipose and infrapatellar fat pad MSCs were capable of differentiating in the chondrogenic direction however exhibited differences in morphology and gene expression status. These findings suggest that the combination of MSCs and the organ-on-a-chip platform could offer a viable alternative to cartilage biopsy for providing deeper insights into individual genetic susceptibilities related to OA and facilitate the development of personalised treatment strategies, paving the way for more effective management of this chronic and often debilitating condition.