Extracellular vesicles in the treatment and prevention of osteoarthritis: can horses help us translate this therapy to humans?

Abstract

Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play a crucial role in the therapeutic efficacy observed with MSCs and offer a potentially novel cell-free therapeutic that may negate many of the concerns with MSCs. There is evidence that EVs have profound anti-inflammatory, immunomodulatory, and pro-regenerative effects equal to or greater than the MSCs they are derived from in the treatment of OA. Most of these studies are in small animal models, limiting the translation of these results to humans. However, highly translational animal models are crucial for further understanding the efficacy of potential therapeutics and for close comparisons with humans. For this reason, the horse, which experiences the same gravitational impacts on joints similar to people, is a highly relevant large animal species for testing. The equine species has well-designed and validated OA models, and additionally, therapies can be further tested in naturally occurring OA to validate preclinical model testing. Therefore, the horse is a highly suitable model to increase our knowledge of the therapeutic potential of EVs.

Plasma and synovial fluid extracellular vesicles display altered microRNA profiles in horses with naturally occurring post-traumatic osteoarthritis: an exploratory study

“…5 Constituting a rapidly expanding field of research, extracellular vesicles (EVs) have been identified to play a major role in both joint homeostasis and the pathophysiology of PTOA in humans and horses. 6,7 EVs are small, membrane-enclosed vesicles that are secreted by most mammalian cells. There are 3 subtypes of EVs that are classified based on their biogenesis and size as exosomes (approx 30 to 100 nm), microvesicles (approx 100 to 1,000 nm), and apoptotic vesicles (approx 1,000 to 5,000 nm).…”