Abstract
Equine mesenchymal stem/stromal cells (MSCs) are multipotent cells that are widely used for treatment of musculoskeletal injuries, and there is significant interest in expanding their application to nonorthopedic conditions. MSCs possess antibacterial and immunomodulatory properties that may be relevant for combating infection; however, comparative studies using MSCs from different origins have not been carried out in the horse, and this was the focus of this study. Our results showed that MSC-conditioned media attenuated the growth of Escherichia coli, and that this effect was, on average, more pronounced for endometrium (EM)-derived and adipose tissue (AT)-derived MSCs than for bone marrow (BM)-derived MSCs. In addition, the antimicrobial lipocalin-2 was expressed at mean higher levels in EM-MSCs than in AT-MSCs and BM-MSCs, and the bacterial component lipopolysaccharide (LPS) stimulated its production by all three MSC types. We also showed that MSCs express interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1, chemokine ligand-5, and Toll-like receptor 4, and that, in general, these cytokines were induced in all cell types by LPS. Low expression levels of the macrophage marker colony-stimulating factor 1 receptor were detected in BM-MSCs and EM-MSCs but not in AT-MSCs. Altogether, these findings suggest that equine MSCs from EM, AT, and BM have both direct and indirect antimicrobial properties that may vary between MSCs from different origins and could be exploited toward improvement of regenerative therapies for horses.
Highlights
Equine mesenchymal stem/stromal cells (MSCs), obtained typically from bone marrow (BM) and adipose tissue (AT), have been used clinically for more than a decade
BM-MSCs, AT-MSCs, and EM-MSCs were obtained each from three horses as described [5,23], and were characterized following the criteria established by the International Society for Cellular Therapy for MSCs [25]
After 16 h of incubation, the wells were washed with phosphate-buffered saline (PBS) and cells harvested into Trizol (Thermo Fisher Scientific), frozen and stored at -80°C before further analysis
Summary
Equine mesenchymal stem/stromal cells (MSCs), obtained typically from bone marrow (BM) and adipose tissue (AT), have been used clinically for more than a decade. MSCs can have different inflammatory phenotypes depending on the extracellular milieu [19]. In a low inflammatory environment or upon activation of Toll-like receptor 4 (TLR4) by bacterial lipopolysaccharide (LPS), MSCs polarize to a proinflammatory state (MSC1), characterized by increased production of chemokines and cytokines that may recruit and activate immune effector cells [19]. MSCs may display an anti-inflammatory phenotype (MSC2)
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