Many alternative treatments aimed at modulating osteoarthritis (OA) progression have been developed in the past decades, including the use of cytokine inhibitors. IL-1β is considered one of the most impactful cytokines in OA disease and therefore, its blockage offers a promising approach for the modulation of OA. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory protein belonging to the IL-1 family that competes with IL-1β for occupancy of its receptors, without triggering the same downstream inflammatory response. Because of its natural anti-inflammatory properties, different methods have been proposed to use IL-1Ra therapeutically in OA. Autologous conditioned serum (ACS) and autologous protein solution (APS) are blood-derived products produced with the use of specialized commercial kits. These processes result in hemoderivatives with high concentrations of IL-1Ra and other cytokines and growth factors with potential modulatory effects on OA progression. Several studies have demonstrated potential anti-inflammatory effect of these therapies with promising clinical results. However, as with any hemoderivatives, clinical outcomes may vary. For optimal therapeutic use, further research is warranted for a more comprehensive understanding of the product's composition and interaction of its components in joint inflammation. Additionally, differences between ACS and APS treatments may not be clear for many clients and clinicians. Thus, the objective of this narrative review is to guide the reader in important aspects of ACS and APS therapies, in vitro and in vivo applications and to compare the use of both treatments in OA.
The emergence of “superbugs” resistant to antimicrobial medications threatens populations both veterinary and human. The current crisis has come about from the widespread use of the limited number of antimicrobials available in the treatment of livestock, companion animal, and human patients. A different approach must be sought to find alternatives to or enhancements of present conventional antimicrobials. Mesenchymal stromal cells (MSC) have antimicrobial properties that may help solve this problem. In the first part of the review, we explore the various mechanisms at work across species that help explain how MSCs influence microbial survival. We then discuss the findings of recent equine, canine, and bovine studies examining MSC antimicrobial properties in which MSCs are found to have significant effects on a variety of bacterial species either alone or in combination with antibiotics. Finally, information on the influence that various antimicrobials may have on MSC function is reviewed. MSCs exert their effect directly through the secretion of various bioactive factors or indirectly through the recruitment and activation of host immune cells. MSCs may soon become a valuable tool for veterinarians treating antimicrobial resistant infections. However, a great deal of work remains for the development of optimal MSC production conditions and testing for efficacy on different indications and species.
In the 1990s, the role of platelets in inflammation and tissue healing was finally recognized. Since then, the clinical use of platelet-derived products (hemocomponents), such as, platelet-rich plasma (PRP), markedly increased. The promise of a more economical option of a disease-modifying treatment led to the intensive and continuous research of PRP products and to its widespread clinical use. A number of protocols and commercial kits have been developed with the intention of creating a more practical and reliable option for clinical use in equine patients. Still, the direct comparison between studies is particularly challenging due to the lack of standardization on the preparation methods and product composition. The incomplete reports on PRP cellular concentration and the poorly designed in vivo studies are additional matters that contest the clinical efficiency of this biomaterial. To overcome such challenges, several in vitro and in vivo studies have been proposed. Specifically, experiments have greatly focused in protocol optimization and its effect in different tissues. Additionally, in vivo studies have proposed different biological products envisioning the upgrade of the anti-inflammatory cytokines trusting to increase its anti-inflammatory effect. The individual variability and health status of the animal, type of tissue and condition treated, and protocol implemented are known to influence on the product's cell and cytokine composition. Such variability is a main clinical concern once it can potentially influence on PRP's therapeutic effects. Thus, lack of qualitative and quantitative evidence-based data supporting PRP's clinical use persists, despite of the numerous studies intended to accomplish this purpose. This narrative review aims to critically evaluate the main research published in the past decade and how it can potentially impact the clinical use of PRP.
BackgroundPlatelet-rich plasma (PRP) as well as other platelet-derived products have been used as a potential disease-modifying treatment for musculoskeletal diseases, such as osteoarthritis (OA). The restorative properties of such products rely mainly on the high concentrations of growth factors, demonstrating encouraging results experimentally and clinically. Yet, the autologous blood-derived nature of the PRP product lead to limitations that precludes it’s widespread use. The main limitations for PRP use are; product variability, the need for minimum laboratory settings in most cases, and the need for storage at low temperatures to preserve its properties. Based on these limitations, the objective of this study was to investigate an allogeneic off-the-shelf platelet lysate (PL) in cartilage exposed to interleukin 1β (IL-1β). For this purpose, blood and cartilage were harvested from eight skeletally mature and healthy horses. Blood was processed into PL aliquots and divided into three groups (Frozen, Freeze-dried and Filtered freeze-dried), used in autologous and allogeneic conditions and in three different concentrations (1.5, 3 and 6-fold). Different PL preparations were then applied in cartilage culture with interleukin-1 beta and cultured for 10 days. Cartilage and media samples were collected and analyzed for total GAG and 35SO4-labeled GAG content.ResultsNo significant differences between the controls and PL groups in cartilage and media were demonstrated. The effects of PL on cartilage matrix were concentration dependent and intermediate concentrations (3-fold) in PL showed increased 35SO4-labelled GAG in cartilage.ConclusionIn conclusion, the allogeneic freeze-dried PL presented equivalent effects compared to frozen autologous PL. Intermediate platelet concentration on average demonstrated improved results, demonstrating less GAG loss compared to other concentrations.
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