Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells

Abstract

In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. NSAIDs at lower concentrations (0.1-1 μM for celecoxib and meloxicam and 10-50 μM for flunixin) exert a positive effect on cell proliferation and migration, while at higher concentrations (10-200 μM for celecoxib and meloxicam and 100-1000 μM for flunixin and phenylbutazone), there is rather a negative influence. While there is hardly any influence on the adipogenic as well as on the chondrogenic MSC differentiation, the osteogenic differentiation potential, as demonstrated with the von Kossa staining, is significantly disturbed. Thus, it can be concluded that the effects of NSAIDs on MSCs are largely dependent on the concentrations used. Additionally, for some differentiation lineages, also the choice of NSAID is critical.

The Morphology and Proliferation Rate of Canine and Equine Adipose Derived Mesenchymal Stem Cells Cultured with Flunixin Meglumine-in vitro

“…This can be explained by different mechanisms of drug metabolism pathways of canine and equine stem cells. Our results partially correlate with Muller et al [2] findings where positive effects of NSAIDs (in lower concentrations) in EqAdMSCs was observed. Those findings strongly correlate with the presence and localization of mMVs on the AdMSCs' surface.…”

“…The role of NSAIDs involves limitation of prostaglandins (PGs) formation, which is responsible for inflammation, swelling, pain and fever [2] . The NSAIDs inhibit the activity of cyclooxygenase (COX) and therefore the production of prostaglandins (PG) and tromboxanes.…”

Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties

“…Enzymatic digestion may negatively affect cellular properties, due to the major alteration of the natural environment of the cells [30], considering that differences in culture conditions also cause alterations of MSC properties [31-33]. However, the impact of differences in the isolation method on MSC characteristics is not yet completely understood [15,19,28,34,35].…”

The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

“…It is well known that these factors are responsible for inflammation, swelling, pain, and fever. Administration of NSAIDs leads to a reduction of histamine and/or bradykinin release, thereby suppressing the ongoing inflammatory response (Müller et al 2011). Although many advantages of NSAIDs have been reported (e.g., non-addictive nature, possibility of prolonged administration, effective pain relief), their application is also associated with many side effects, such as gastric ulcers, nephrotoxicity, and digestive disorders (Simons et al 2004, Crofford 2013).…”