Engineering of MSC-Derived Exosomes: A Promising Cell-Free Therapy for Osteoarthritis

Abstract

Osteoarthritis (OA) is characterized by progressive cartilage degeneration with increasing prevalence and unsatisfactory treatment efficacy. Exosomes derived from mesenchymal stem cells play an important role in alleviating OA by promoting cartilage regeneration, inhibiting synovial inflammation and mediating subchondral bone remodeling without the risk of immune rejection and tumorigenesis. However, low yield, weak activity, inefficient targeting ability and unpredictable side effects of natural exosomes have limited their clinical application. At present, various approaches have been applied in exosome engineering to regulate their production and function, such as pretreatment of parental cells, drug loading, genetic engineering and surface modification. Biomaterials have also been proved to facilitate efficient delivery of exosomes and enhance treatment effectiveness. Here, we summarize the current understanding of the biogenesis, isolation and characterization of natural exosomes, and focus on the large-scale production and preparation of engineered exosomes, as well as their therapeutic potential in OA, thus providing novel insights into exploring advanced MSC-derived exosome-based cell-free therapy for the treatment of OA.

Keywords: cartilage regeneration; engineering; exosomes; mesenchymal stem cell; osteoarthritis.

Figure 1

Methods for exosome isolating. ILV, intraluminal vesicles; MVB, multivesicular bodies.

Figure 2

Techniques for large-scale exosome production. (A) Large-scale cell culture platforms. They include planar multilayered stack systems, stirred suspension bioreactors and perfusion-based bioreactors (e.g., hollow fiber bioreactor). (B) Increasing single cell secretion of exosomes. The methods mainly include stimulating the cells (e.g., hypoxia) and disrupting cell membranes (e.g., extrusion).

Figure 3

Processing and application of engineered exosomes for osteoarthritis (OA) treatment. (A) Preparation techniques for engineering exosomes. The processing methods include pretreatment of parent cells, drug loading and surface modification. (B) Application of engineered exosomes for OA. The engineered exosomes are administrated to the OA joint through intra-articular injection or scaffold implantation and exert their regulatory effects on bone marrow mesenchymal stem cells (BMSCs), chondrocytes and synoviocytes. As a result, the exosome-based therapy can suppress OA progress and accelerate cartilage regeneration to restore OA joint.