Mylène Jansen

204 Chapter 10 Future directions KJD is able to improve clinical results and promote tissue restoration, and more and more is known about the underlying molecular mechanisms, but there are several steps that could and should be taken in the future (Table 2). While on a group level patients show significant and long-lasting clinical improvement, it is important to realize that individually not all patients respond well. Better KJD treatment response has been shown in male patients and those with more severely affected joints, but might also be related to processes or characteristics not yet known or investigated. Improving patient selection before treatment is crucial to increase the chance patients respond well to the treatment. Also, more patient-specific treatment alterations or combinations with other remedies could be considered. Furthermore, more wide implementation in regular clinical care is required. Thus far, KJD has been applied almost exclusively in trial conditions, and has been used in regular care conditions only in a limited number of hospitals in The Netherlands. Internationally, both patients and surgeons are interested in KJD, but implementing a new treatment in a more widespread clinical setting is a slow and challenging process. Some steps have been made, such as the development of a dedicated device for KJD treatment, but necessary future advances include defining an ideal and official treatment and rehabilitation protocol and arranging treatment reimbursement. Despite the developments in recent years, still a better understanding of the workingmechanisms is warranted. Our knowledge could be improved with use of more novel imaging techniques, such as 7T MRI scans using advanced protocols (e.g. gagCEST or sodium MRI scanning), ideally in combination with SF marker evaluation. These measures could improve patient selection as well. Also other local or systemic markers could be considered. More recently, the role of miRNAs and extracellular vesicles in relation to senescent cells in osteoarthritis is recognized 105 . It might well be that KJD also influences these processes and are part of the mechanism. Moreover, the role of unloading should be further studied implementing tools like advanced gait analysis during and after treatment and computational modeling. Also, the involvement of MSCs needs further studying. Though the first results were focused on involvement of synovial fluid derived MSCs, these cells might originate from the synovial tissue. Cartilage-resident progenitors could be involved as well and become activated and senescent/dying chondrocytes could be cleared upon such stimulation as well. Subsequently, the different components of KJD treatment and the joint processes that are observed as a result could be translated to other treatments that thus far have not shown the desired treatment result.