2021
DOI: 10.1111/vsu.13628
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Toll‐like receptor activation of equine mesenchymal stromal cells to enhance antibacterial activity and immunomodulatory cytokine secretion

Abstract: Objective: To evaluate effects of Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor (TLR, NLR) ligand stimulation of equine mesenchymal stromal cells (MSCs) on antibacterial and immunomodulatory properties in vitro. Study Design: Controlled laboratory study. Sample Population: Equine bone-marrow-derived MSCs (three horses). Methods: MSCs were stimulated with TLR (polyinosinic:polycytidylic acid [pIC] and lipopolysaccharide [LPS]) and NLR agonists (γ-D-Glu-mDAP [IE-DAP]) for 2 h, and p… Show more

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Cited by 24 publications
(38 citation statements)
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References 81 publications
(249 reference statements)
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“…Mesenchymal stromal cells (MSC) express immunomodulatory and antimicrobial properties through paracrine recruitment of immune effector cells and antimicrobial peptide secretion. Pre-activation of human, canine and equine MSC with Toll-like receptor (TLR) agonists such as polyinosinic-polycytidylic acid (polyI:C) has been shown to enhance bacterial killing and increase bacterial clearance in rodent Staphylococcal biofilm infection models [ 97 , 98 , 99 ]. This group of collaborators built further on that work to demonstrate that intra-articular administration of TLR3 polyI:C activated mesenchymal stromal cell therapy improved outcomes in treatment of multidrug resistant septic arthritis in an equine model, with reduced quantitative bacterial counts and pro-inflammatory biomarkers in synovial fluid, improved imaging (ultrasound and magnetic resonance imaging) scores and more rapid normalization of clinicopathologic parameters both systemically and in synovial fluid.…”
Section: Ongoing Investigations In the Role Of Innate Immunity In Oa Progressionmentioning
confidence: 99%
“…Mesenchymal stromal cells (MSC) express immunomodulatory and antimicrobial properties through paracrine recruitment of immune effector cells and antimicrobial peptide secretion. Pre-activation of human, canine and equine MSC with Toll-like receptor (TLR) agonists such as polyinosinic-polycytidylic acid (polyI:C) has been shown to enhance bacterial killing and increase bacterial clearance in rodent Staphylococcal biofilm infection models [ 97 , 98 , 99 ]. This group of collaborators built further on that work to demonstrate that intra-articular administration of TLR3 polyI:C activated mesenchymal stromal cell therapy improved outcomes in treatment of multidrug resistant septic arthritis in an equine model, with reduced quantitative bacterial counts and pro-inflammatory biomarkers in synovial fluid, improved imaging (ultrasound and magnetic resonance imaging) scores and more rapid normalization of clinicopathologic parameters both systemically and in synovial fluid.…”
Section: Ongoing Investigations In the Role Of Innate Immunity In Oa Progressionmentioning
confidence: 99%
“…The increasing incidence of antibiotic resistance has driven the investigation of novel biological therapies with antimicrobial properties, including platelet-rich plasma lysate and mesenchymal stromal cells. [78][79][80][81][82] Recent literature describes the formation of free-floating biofilm aggregates by Staphylococcus aureus and other gram-positive and -negative isolates that are most frequently reported to be involved in human septic arthritis (Streptococcus zooepidemicus, Escherichia coli and Pseudomonas aeruginosa) in synovial fluid, rendering them more tolerant to antibiotic therapy compared with their planktonic form. 78 The equine model of septic arthritis and availability of equine synovial fluid for use in in vitro assays makes the horse a valuable translational model to study the host-pathogen interactions in human septic arthritis as well, compared with the more difficult to source synovial fluid from healthy human individuals.…”
Section: Supplemental Intr A-arti Cul Ar Ther Apie S To Antib I Oti C S To Tre At Joint Infec Tionmentioning
confidence: 99%
“…Mesenchymal stromal cells (MSC) exert potent immunomodulatory and antibacterial activities, making them attractive as biological therapies for diverse conditions, including musculoskeletal injuries, wound healing and bacterial infections. 80,82,[91][92][93][94][95][96] Equine MSC were initially demonstrated to inhibit the growth of Escherichia coli and Staphylococcus aureus through antimicrobial peptide secretion and depolarisation of cell membranes. 81 Their application in the treatment of infection is gaining increasing attention and methods to optimise antibacterial activity have been further explored.…”
Section: Mesenchymal Stromal Cellsmentioning
confidence: 99%
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