uKNEEversal: a miniaturized 3D in vitro model of human joint to gain new knowledge on Osteoarthritis pathophysiology

Description du projet

Un modèle d’organe sur puce pour l’ostéoarthrite

L’ostéoarthrite (OA) est une maladie dégénérative des articulations qui entraîne un handicap important. Les traitements pharmacologiques existants sont symptomatiques et ne permettent pas d’inverser la pathologie. Le principal objectif du projet uKNEEversal, financé par l’UE, est de développer un modèle in vitro d’OA capable de reproduire la complexité de la maladie et pouvant être utilisé pour étudier les mécanismes sous‑jacents de l’OA. Les chercheurs utiliseront des organes humains sur puce reproduisant étroitement et fidèlement la fonction des organes natifs dans un environnement miniaturisé et contrôlé. La technologie d’organe sur puce permettra de générer un modèle d’articulation in vitro de l’OA humaine capable de prédire la réponse à des médicaments spécifiques.

Objectif

uKNEEversal aims at generating a comprehensive in vitro human model of Osteoarthritis (OA) to fill lacks of existing pre-clinical tools and open perspectives to investigate OA mechanisms and therapies. Degenerative joint diseases, among which OA is the most prevalent, represent the second cause of disability worldwide. Available pharmacological options are limited and focus on the reduction of symptoms, being unable to factually reverse the pathology. One of the major obstacles towards the development of disease-reversing therapies is the gap of knowledge on OA mechanisms, linked to the lack of reliable OA pre-clinical models. Existing pre-clinical tools are currently not able to dissect OA complexity in terms of cross talks among compartments and molecular pathways affected. Although animal models may offer a complex enough model, they often fail in predicting typical human responses and recent legislation about 3R principle is pushing Pharma towards methods alternative to animals. In this regards, one ground-breaking goal in the field is the generation of an OA model able to reflect the complexity of the disease in vitro. To date, most in vitro OA models, based on traditional 2D and macroscale culture systems, are affected by sampling sites, poor scalability, and are too simplistic to recapitulate joint 3D architecture. As an alternative, human organs-on-chips (OOC) have been claimed able to transform many areas of basic research and drug development. OOC are in vitro tools that can recapitulate a human organ’s function better than traditional culture systems, in a miniaturized environment. Miniaturization has indeed showed an enhanced control leading to in vitro models recapitulating the native organ functions with accuracy hardly achievable at the macroscale.
In this scenario, uKNEEversal aims at filling the gap of existing poorly predictive pre-clinical models generating an in vitro human osteoarthritic joint model through organs-on-chip technology.