Extracellular vesicles from synovial fluid-derived mesenchymal stem cells confer chondroprotective effects on in vitro and in vivo osteoarthritic chondrocytes

Abstract

Introduction

Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs) are theorized to mediate cartilage regeneration through paracrine actions. It is hypothesized that EVs derived from synovial fluid MSCs (SF-MSCs) will promote anabolic gene expressions and decrease catabolic markers of in vitro osteoarthritic chondrocytes. These EVs will also demonstrate increased cartilage regeneration as measured in a rat osteoarthritis (OA) model.

Objectives

This study tested the in-vitro anti-inflammation effects of using EVs from SF-MSCs on chondrocytes and in vivo study on chondroprotective effects of EVs with OA environment.

Methods

In vitro, rat chondrocytes were exposed to EVs collected from SF-MSC that had been either exposed or unexposed to interleukin-1β (IL-1β). Gene expressions for various anabolic and catabolic markers were measured. In vivo, rats who received anterior cruciate ligament transection as an OA model with an osteoarthritic knee joint were exposed to weekly injections of SF-MSC-derived EVs at 2 different doses. The results were evaluated with histological study and scored using the Osteoarthritis Research Society International system. Serum cytokines were analyzed via enzyme-linked immunosorbent assay.

Results

In vitro, chondrocytes exposed to SF-MSCs derived EVs demonstrated increased anabolic markers and decreased catabolic markers also with the EVs collected from interleukin-1β treated SF-MSCs. In vivo, rats that received EVs displayed lower Osteoarthritis Research Society International scores, more collagen type II alpha 1, and less matrix metalloproteinase-13 than the control groups. This anti-inflammation potential was systemic, as demonstrated by the decrease of serum proinflammatory cytokines.

Conclusions

SF-MSCs-derived EVs were effective at promoting the expression of anabolic markers while simultaneously attenuating the production of proinflammatory markers in vitro and in vivo. These anti-inflammation effects were dose-dependent in vivo. The injection of EVs in the knee joint changed the cytokines in the serum.