Abstract
BackgroundIn athlete horses, suspensory ligament (SL) injuries are the most common cause of lameness. Healing of SL injury is still problematic, and even proper rehabilitation and pharmacological therapy do not guarantee returning to the initial performance level. In our previous studies, we have shown that a combination of 5-azacytidine (AZA) and resveratrol (RES) exerts beneficial, rejuvenating effects on metabolic syndrome derived adipose-derived stem cells (ASCs). Thus, in the presented research, we investigate whether not only rejuvenated ASC but also microvesicles (MVsAZA/RES) secreted by them possess enhanced regenerative properties in SL injury.MethodsIn the presented study, a 6-year-old Dutch Warmblood gelding, working in jumping, was diagnosed with SL injury using ultrasonography, Doppler, real-time elastography and thermography. As a therapeutic strategy, the affected animal was treated with extracellular microvesicles derived from ASC treated with the combination of 5-azacytydine (AZA) and resveratrol (RES) (MVsAZA/RES).ResultsFirst, anti-apoptotic effects of MVsAZA/RES were tested in co-culture with metabolic syndrome derived ASC. The proliferation of cells and expression of pro-apoptotic genes were investigated. Then, MVsAZA/RES were injected directly into the injured SL of the Dutch Warmblood gelding. In vitro assays revealed that MVsAZA/RES enhance the proliferation of ASC and exert an anti-apoptotic effect. In the affected horse, the application of MVsAZA/RES resulted in increased lesion filling and improvement of angiogenesis and elasticity in injured tissue.ConclusionsAs MVsAZA/RES mimic several of the biological actions exerted by ASC, they have become an alternative for stem cell-based therapies and can be effectively applied for the treatment of SL injury in horses.
Highlights
In athlete horses, suspensory ligament (SL) injuries are the most common cause of lameness
Our previous studies have shown that a combination of 5-azacytydine (AZA) and resveratrol (RES) reverses aged phenotype of mesenchymal stem cells (MSCs) isolated from equine metabolic syndrome diagnosed animals (MSC-EMS) [26,27,28]
Our group has revealed for the first time that in horses diagnosed with equine metabolic syndrome (EMS), isolated adipose-derived stem cells (ASCs) suffers from great impairment of their cytophysiological properties [32]
Summary
Suspensory ligament (SL) injuries are the most common cause of lameness. Healing of SL injury is still problematic, and even proper rehabilitation and pharmacological therapy do not guarantee returning to the initial performance level. Local muscle or tendon trauma occurs leading to poor performance and lameness. Horses affected with strains, depending on its severity, are provided with anti-inflammatory, muscle relaxants and non-steroidal drugs while exercise activity is reduced from days to months [6]. Suspensory ligament (SL) damage in horses is the most common cause of lameness especially in athletic individuals in competing dressage. Healing of SL injury is still problematic, and even proper rehabilitation does not guarantee returning to the initial performance level. Application of platelet-rich plasma (PRP) and stem cell therapies is more and more common [9, 10]
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