Abstract
Mesenchymal stem/stromal cells (MSCs) are increasingly explored for the treatment of degenerative and inflammatory diseases in human and veterinary medicine. One of the key characteristics of MSCs is that they modulate inflammation mainly through the secretion of soluble mediators. However, despite widespread clinical use, knowledge regarding the effector mechanisms of equine MSCs, and consequently their effectiveness in the treatment of diseases, is still unknown. The objectives of this study were to determine the mechanisms underlying inhibition of lymphocyte proliferation by equine bone marrow-derived MSCs, and to evaluate the effect of pre-conditioning of equine MSCs with different pro-inflammatory cytokines on inhibition of lymphocyte proliferation. We determined that inhibition of lymphocyte proliferation by equine MSCs depends on activity of prostaglandin-endoperoxide synthase 2 and indoleamine 2,3-dioxygenase. Additionally, pre-conditioning of MSCs with TNF-α, IFN-γ or their combination significantly increased the expression of prostaglandin-endoperoxide synthase 2, indoleamine 2,3-dioxygenase, iNOS and IL-6. This upregulation correlated with an increased inhibitory effect of MSCs on lymphocyte proliferation. In conclusion, pre-conditioning of bone marrow-derived MSC increases their inhibitory effect on lymphocyte proliferation in horses.
Highlights
Multipotent mesenchymal stem/stromal cells (MSCs) are a heterogeneous fibroblastic-like subset of cells originally obtained from the stromal compartment of bone marrow (BM) [1, 2]
In order to determine the role of important molecular pathways commonly involved in the inhibitory effect of MSCs on lymphocyte proliferation in different species, we explored the role of prostaglandin E2 (PGE2), IDO and inducible form of nitric oxide synthetase (iNOS) by using pharmacological inhibition of these molecules during peripheral blood mononuclear cells (PBMC): MSCs co-culture
It is already known that MSCs can inhibit lymphocyte proliferation, regardless of the species or the site of obtention [11, 51,52,53,54,55]
Summary
Multipotent mesenchymal stem/stromal cells (MSCs) are a heterogeneous fibroblastic-like subset of cells originally obtained from the stromal compartment of bone marrow (BM) [1, 2]. Pre-conditioning: Increasing Equine MSCs Immunomodulation and adipocytes [8]. This allows MSCs to be involved in tissue reparation and regeneration of injured tissue [9, 10]. MSCs are able to modulate different components of the immune response, either of the innate or adaptive system, apparently without compromising the response against pathogens [13,14,15]. Another important feature of MSCs is they are hypoimmunogenic and can be safely administered to allogeneic hosts [16]
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