Résumé
Osteoarthritis is the most prevalent degenerative and inflammatory rheumatic disorders in developed countries, yet no efficient disease-modifying drugs are currently available. Mesenchymal stem cells (MSC) have generated significant medical considerations since they exhibit tissue-regenerative and immunomodulatory properties. However, despite their promising effects in preclinical models of OA, MSC therapeutic potential in clinic has not been clearly proven yet. Among the identified limits, differences between animal models and human immune system are pointed out. The generation of immunodeficient Il2rg-/- mice have pave the way to the development of humanized mice, displaying human immune system. Those animal models could therefore improve the translation from preclinical data to clinic.Recently, it was also demonstrated that modulation of nuclear receptor PPARβ/δ in murine bone marrow MSC improves their immunosuppressive properties in vitro and their therapeutic effects in an experimental model of arthritis. Considering the importance of inflammation in the pathophysiology of osteoarthritis and the immunomodulatory potential of MSCs, our objectives were, firstly, to develop a preclinical model of osteoarthritis in humanized mice, allowing a better translation for preclinical data to the clinic. Then, we investigated whether modulation of PPARβ/δ could improve the MSC therapeutic properties in osteoarthritis.