Breakfast Workshop A: 3R Approaches in OA: Human Joint Explant Models for Preclinical Research

Date/Time: Friday, April 8, 2022 - 7:30 AM to 8:30 AM
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3R Approaches in OA: Human Joint Explant Models for Preclinical Research

Discovery of novel drug targets and preclinical evaluation of disease-modifying OA drugs (DMOAD) rely predominantly on the use of in vitro models, such as human or murine chondrocytes, or experimental murine models. However, intrinsic limitations of these models pose serious challenges to translating preclinical findings into clinical practice.

For example, whereas different clinical phenotypes are known in humans (e.g. inflammatory, metabolic and biomechanical OA), experimental models are predominantly surgically-induced corresponding with post-traumatic OA. Furthermore, the vast majority of in vivo models are focused on knee OA, yet validated models for spine, hand and hip OA are lacking. In addition, the relatively small size of murine joints complicates the assessment of bone marrow lesions and synovitis by magnetic resonance imaging, which are important diagnostic and prognostic imaging biomarkers in clinical studies. Experimental in vitro studies with chondrocytes and osteoblast provide valuable insight into cellular responses, but do not take the crosstalk between different joint tissues into account.

Tissue culture of human clinical specimens ex vivo (e.g. osteochondral plugs) permits studies of pathogenic processes and evaluation of DMOAD treatment effects in a heterogeneous setting, in which structural and molecular tissue alterations are preserved. In this workshop, we will review the principles of osteochondral explant models and provide valuable tips and tricks on tissue sampling and downstream assays in OA research.