Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix

Abstract

BackgroundMesenchymal stem cell therapy for osteoarthritis (OA) has been widely investigated, but the mechanisms are still unclear. Exosomes that serve as carriers of genetic information have been implicated in many diseases and are known to participate in many physiological processes. Here, we investigate the therapeutic potential of exosomes from human embryonic stem cell-induced mesenchymal stem cells (ESC-MSCs) in alleviating osteoarthritis (OA).MethodsExosomes were harvested from conditioned culture media of ESC-MSCs by a sequential centrifugation process. Primary mouse chondrocytes treated with interleukin 1 beta (IL-1β) were used as an in vitro model to evaluate the effects of the conditioned medium with or without exosomes and titrated doses of isolated exosomes for 48 hours, prior to immunocytochemistry or western blot analysis. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of C57BL/6 J mice as an OA model. This was followed by intra-articular injection of either ESC-MSCs or their exosomes. Cartilage destruction and matrix degradation were evaluated with histological staining and OARSI scores at the post-surgery 8 weeks.ResultsWe found that intra-articular injection of ESC-MSCs alleviated cartilage destruction and matrix degradation in the DMM model. Further in vitro studies illustrated that this effect was exerted through ESC-MSC-derived exosomes. These exosomes maintained the chondrocyte phenotype by increasing collagen type II synthesis and decreasing ADAMTS5 expression in the presence of IL-1β. Immunocytochemistry revealed colocalization of the exosomes and collagen type II-positive chondrocytes. Subsequent intra-articular injection of exosomes derived from ESC-MSCs successfully impeded cartilage destruction in the DMM model.ConclusionsThe exosomes from ESC-MSCs exert a beneficial therapeutic effect on OA by balancing the synthesis and degradation of chondrocyte extracellular matrix (ECM), which in turn provides a new target for OA drug and drug-delivery system development.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0632-0) contains supplementary material, which is available to authorized users.

Exosomes in Inflammation and Inflammatory Disease

“…The therapeutic effect of MSC‐derived exosomes on arthritis have also been investigated. In several studies, intravenous or intra‐articular exosomes isolated from MSCs were shown to inhibit macrophage activation, inflammation, and cartilage destruction in in vitro and in vivo models via inhibition of catabolisis, inflammatory markers and apoptosis, increase of collagen type II synthesis, and modulation of T and B cells …”

Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy

“…Immunohistochemical staining was conducted following a standard protocol (Y. Wang, Yu, Liu, et al, 2017). Cartilage matrix was detected using type II collagen (COL II) and aggrecan.…”

Exosomes from tendon stem cells promote injury tendon healing through balancing synthesis and degradation of the tendon extracellular matrix

“…Haomin Cui et al reported that exosomes containing miRNA derived from macrophages induce peritendinous fibrosis healing after tendon injury. Yafei Wang and S. Zhang et al revealed that exosomes from embryonic MSCs alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Myeongsik Oh et al illustrated that exosomes derived from human induced pluripotent stem cells ameliorate the aging of skin fibroblasts.…”