Local and systemically administered mesenchymal cells regenerative capacity on osteoartrhitis animal model

Abstract

Osteoarthritis (OA), a significant problem for Public Health, manly related to aging, causes articular cartilage (CA) degeneration, joint pain and consequently locomotion disability. This process is accompanied by increased presence of inflammatory cytokines and proteolytic molecules in the tissue, leading to extracellular matrix degeneration and decreased CA function. Current therapies for treatment of OA are limited and unsatisfactory, leading to formation of fibrocartilaginous tissue with inferior biomechanics characteristics. Regenerative cartilage research has focused on mesenchymal stem cells (MSC) therapy, which have been identified as a potential source for regeneration of various tissues, including cartilage. Although, further investigation is required to establish a consensus on the best cell route administration for OA treatment. The aim of this project is to evaluate two different MSC route administrations, intravenous and intra-articular, related to cartilage regeneration. Rat OA model, induced surgically by destabilization of medial meniscus ligament (DMM) will be used. MSC expressing luciferase and red fluorescent protein administration will allow cell localization will by in vivo (bioluminescence) imaging. Regenerative and function capacity will be assessed by articular tissue histological and gait analyses, respectively. Pro and anti-inflammatory cytokines present in blood plasma and synovial fluid will be measured. Our hypothesis is that MSC intravenous and intra-articular administrations improve cartilage regeneration, by different pathways due to an initial systemic anti-inflammatory response followed by migration of MSC to the injury site, and improving the local microenvironment. We believe, that our findings, will offer support for future studies about MSC therapy for OA treatment. (AU)