Introduction

Degenerative meniscal tears are the most common meniscal lesions, representing huge clinical and socio-economic burdens. Their role in knee osteoarthritis (OA) onset and progression is well established and demonstrated by several retrospective studies. Effective preventive measures and non-surgical treatments for degenerative meniscal lesions are still lacking, also because of the lack of specific and accurate animal models in which test them. Thus, we aim to develop and validate an accurate animal model of meniscus degeneration.

No therapeutic strategy, administered in the early stage of osteoarthritis (OA), is fully able to block the degenerative and inflammatory progress of the pathology, whose only solution remains surgery. Aiming to identify minimally invasive therapies able to act on both degenerative and inflammatory processes, infiltrative treatments based on mesenchymal stem cells represent a promising solution due to their proliferative, immunomodulatory, anti-inflammatory, and paracrine ability. Accordingly, the aim of the present study was to investigate the performance of different cell therapies (stem cells from adipose tissue, ADSCs, stromal vascular fraction, SVF, and culture expanded, AECs vs negative control NaCl) in the treatment of OA. An in vivo model of early OA was developed in sheep knee (research protocol N.62/2018-PR date 29/01/2018 approved by the local Ethical Committee). Three and six months after the treatments injections, gross evaluation of articular surfaces (damage score, DS), histological (cartilage thickness, Th; fibrillation index, FI; collagen II content, C2) and mechanical assessment (elastic modulus, E; stress-relaxation time, τ) of cartilage were carried out. Due to the importance of the relationship between structure/composition (histology) and function (mechanics), this study investigated which of the revealed parameters were involved in such relation and how they were influenced by the level of degeneration and by the specific cell treatment, thus to better understand cell-tissue interaction.

A statistically significant multi-variable linear regression model was found between τ and Th, FI, C2 (R2 0.7, p-value 8.39E-5). The relation was particularly strong between τ and C2 (p-value 7E-4), with a positive coefficient of 0.92. This is in agreement with literature, where a higher cartilage viscosity was related to a major content of collagen. By dividing the samples in two groups depending on cartilage damage, the more degenerated group (DS > 5) showed statistically significant lower C2 (p-value 0.0124) and τ (p-value 0.05), confirming that collagen content and viscosity decrease with OA grade increasing. Averaging the entire group of samples, the OA degeneration progressed between 3 and 6 months after, and despite, the treatment. But focusing on specific treatments, SVF and AECs differed from the general trend, inducing a higher amount of collagen at 6 months respect to 3 months. Moreover, articular cartilage treated by AECs and, overall, SVF showed a higher content of collagen and a major viscosity respect to the other treatments.

We conclude that an injection of mesenchymal stem cells from stromal vascular fraction in early OA articulations could hinder the degenerative process, preserving or even restoring collagen content and viscosity of the articular cartilage.