Retinoic acid-mediated anti-inflammatory responses in equine immune cells stimulated by LPS and allogeneic mesenchymal stem cells

Abstract

Retinoic acid (RA), an active metabolite of vitamin A, has shown potential therapeutic immunomodulatory properties. Allogeneic mesenchymal stem cells (MSCs)-based therapy is an effective approach to induce tissue healing and regeneration in many equine orthopedic conditions. However, MSCs-based therapies induced inflammatory responses in vivo. This study aimed to: 1. Determine the effect of RA cell culture treatment on inflammatory responses of lipopolysaccharides (LPS)- and allogeneic MSCs-stimulated peripheral blood mononuclear cells (PBMCs). 2. Determine the effect of RA on stimulated MSCs viability and morphology. Allogeneic MSCs-stimulated PBMCs had significant decreases in the anti-inflammatory cytokines (IL-10, IL-1ra, TGF-β1), increases in the pro-inflammatory mediators (IL-1β, IL-6, TNF-α, SAA), and increases of CD14 and MHC II percent positive cells compared to LPS- and non-stimulated PBMCs. Retinoic acid treatment of LPS- and allogeneic MSCs-stimulated PBMCs counterbalanced the induced inflammatory responses. Moreover, RA significantly improved the viability and morphology of stimulated MSCs. These findings highlighted the potential complications of equine allogeneic MSCs-based therapies and the immuno-modulatory effect of RA on equine stimulated cells. In conclusion, the use of RA to ameliorate allogeneic MSCs therapy associated inflammation may offer advantages that would require further investigations.

Keywords: Cytokines; Horse; Immunomodulation; Inflammation; MHC molecules; PBMCs; Transplantation.