The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

Abstract

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

Anti-inflammatory and immunomodulatory effects of the extracellular vesicles derived from human umbilical cord mesenchymal stem cells on osteoarthritis via M2 macrophages

“…And the therapeutic roles of hUCMSCs-EVs on OA were superior to those of PRP, which is applied with increasing frequency to treat musculoskeletal pathologies, such as OA, by intra-articular injection [ 29 ]. These results are consistent with those of EVs derived from BMMSCs, ADSCs, and ESCs on the treatment of OA [ 30 – 32 ]. Therefore, together with our results, these findings further prove that the EVs derived from different stem cells appear to possess a special effect of alleviating OA.…”

Exosomes in the Pathogenesis, Progression, and Treatment of Osteoarthritis

“…In addition to BMSC, embryonic stem cell-derived MSCs (ESC-MSCs) [40], synovial MSCs (SMSC) [37,38], adipose-derived MSCs (ADSC) [21,62], umbilical cord mesenchymal stem cells (UC-MSCs) [42], periodontal ligament-derived stem cells (PDLSCs) [63], amniotic fluid stem cells (AFSCs) [46], and IPFP-MSCs [44,64,65] are other important origins of MSC-derived exosomes in OA treatment [38]. IA injection of ESC-MSC-derived exosomes facilitated the repair of osteochondral defects, maintained the chondrocyte phenotype, promoted cartilage formation, reduced matrix degradation, and impeded cartilage destruction both in vitro and in the destabilization of medial meniscus (DMM)-induced OA model in mice [40,66]. Mechanistically, these effects were achieved by promoting chondrocyte proliferation and migration, increasing collagen type II synthesis, and decreasing ADAMTS5 (A disintegrin and metalloproteinase with thrombospondin motifs 5) expression [40].…”

“…However, direct delivery of exosomes, such as IA or subcutaneous injections, is associated with quick clearance in vivo and limited effective period [138]. Chondrocyte-targeted drug delivery is even more challenging due to the biological barrier formed by a dense matrix of proteoglycans, collagen, and highly negatively charged glycosaminoglycans in the cartilage [66], which requires more exosomes in a higher concentration. To improve yield, elongate retention time, and optimize treatment effects, several strategies have been proposed and studied, such as the development of exosome-mimetic nanovesicles (EMNVs), alteration of the culture condition, membrane surface modification, and controlled release with biomaterial platforms [103,139].…”

Small Extracellular Vesicles Derived from Human Chorionic MSCs as Modern Perspective towards Cell-Free Therapy

“…Internalization of exosomes into the cells is considered to be one of the mechanisms of cargo delivery to recipient cells and, as such, affects their fate [70,71], however, the precise mechanism of these proceedings is not well understood and is still under examination. Currently it is known that exosomal content is connected to the therapeutic effect of MSCs-derived exosomes, most evident in the repair and regeneration of injured tissue during the osteoarthritic process (OA) [72,73]. Specifically, exosomes derived from different types of MSCs can protect the OA joint from damage by supporting cartilage repair, inhibiting synovitis and mediating subchondral bone remodeling, as well as have been demonstrated to regulate cartilage regeneration and to attenuate OA progression in certain models [27,72,[74][75][76][77].…”