The Use of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles in the Treatment of Osteoarthritis: Insights from Preclinical Studies

Abstract

Osteoarthritis (OA) is a prominent cause of disability, and has severe social and economic ramifications across the globe. The main driver of OA's pervasiveness is the fact that no current medical interventions exist to reverse or even attenuate the degeneration of cartilage within the articular joint. Crucial for cell-to-cell communication, extracellular vesicles (EVs) contribute to OA progression through the delivery of bioactive molecules in the inflammatory microenvironment. By repurposing this acellular means of signal transmission, therapeutic drugs may be administered to degenerated cartilage tissue in the hopes of encouraging regeneration. Positive outcomes are apparent in in vivo studies on this subject; however, for this therapy to prove itself in the clinical world, efforts towards standardizing the characterization, application, biological contents, and dosage are essential.

Keywords: cartilage regeneration; inflammation attenuation; mesenchymal stem/stromal cell-derived extracellular vesicles; osteoarthritis.

Figure 1

Potential advantages for MSC-EV therapy (blue) compared to platelet-rich plasma (PRP) and MSC therapies (red). PRP is a constituent of a patient’s blood (IA injected) that possesses large concentrations of platelets and regenerative factors. The source, basic description, and challenges for each therapy are given, as well as their derivation. Two of the main challenges involved in the PRP approach are circumvented by MSC-EV treatment, due to EVs being primarily donor-independent and grown and produced under good manufacturing practice (GMP) conditions. The potential tumorigenicity of MSC therapy is subverted using acellular particles instead of living cells. From this, the ability to produce EVs from immortalized cell lines instead of primary cells also reduces the batch-to-batch variability of the product. Although PRP and MSC therapy have received a greater deal of research in clinical trials, MSC-EVs have begun to undergo stage 1–2 clinical trials in OA therapeutics. Image taken from Biorender.