{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T18:24:29Z","timestamp":1784312669556,"version":"3.55.0"},"reference-count":40,"publisher":"American Veterinary Medical Association (AVMA)","issue":"S1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>To investigate mechanistically the reported beneficial effects of immune-activated mesenchymal stromal cell (MSC) therapy to treat equine septic arthritis, leveraging Nanostring technology.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>ANIMALS<\/jats:title>\n<jats:p>8 Quarter Horses with induced tibiotarsal <jats:italic>Staphylococcus aureus<\/jats:italic> septic arthritis treated IA with either Toll-like receptor-3 agonist polyinosinic:polycytidylic acid\u2013activated MSCs + vancomycin antimicrobials (TLR-MSC-VAN; n = 4) or antimicrobials (VAN; 4).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>METHODS<\/jats:title>\n<jats:p>Synovial tissues were collected and fixed in neutral-buffered 10% formalin, and formalin-fixed paraffin-embedded synovial and osteochondral tissues were sequenced using a custom-designed 200-gene equine Nanostring nCounter immune panel to directly quantify expression of key immune and cartilage-related genes. Immunohistochemistry to detect CD3+ T cells was performed on synovial tissues to further quantify T-cell infiltration in TLR-MSC-VAN\u2013 versus VAN-treated joints.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>Comparison of synovial transcriptomes between groups revealed moderate changes in differential gene expression, with upregulated expression of 9 genes and downregulated expression of 17 genes with fold change \u2265 2 or \u2264 \u22122 and a significant false discovery rate\u2013adjusted <jats:italic>P<\/jats:italic> value of \u2264 .05. The most upregulated genes in TLR-MSC-VAN\u2013treated horses included those related to T-lymphocyte recruitment and function, while pathways related to innate immune activation and inflammation were significantly downregulated. Immunohistochemistry and quantitation of CD3+ T-cell infiltrates revealed a numerically greater infiltrate in synovial tissues of TLR-MSC-VAN\u2013treated horses, which did not reach statistical significance in this small sample set (<jats:italic>P<\/jats:italic> = .20).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>CLINICAL RELEVANCE<\/jats:title>\n<jats:p>Targeted transcriptomic analyses using an equine Nanostring immune and cartilage health panel provided new mechanistic insights into how innate and adaptive immune cells within synovial tissues respond to TLR-activated MSC treatment when used to treat septic arthritis.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/javma.23.10.0561","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T14:44:31Z","timestamp":1706712271000},"page":"S73-S82","source":"Crossref","is-referenced-by-count":4,"title":["Targeted transcriptomic analysis of synovial tissues from horses with septic arthritis treated with immune-activated mesenchymal stromal cells reveals induction of T-cell response pathways"],"prefix":"10.2460","volume":"262","author":[{"given":"Lynn M.","family":"Pezzanite","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndah","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie B.","family":"Engiles","sequence":"additional","affiliation":[{"name":"Departments of Pathobiology and Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Plaisance","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie R.","family":"Goodrich","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Dow","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"},{"name":"Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"B1","series-title":"Equine Vet Educ","first-page":"284","article-title":"Dosing equine antimicrobials: ensuring clinical success and avoiding antimicrobial resistance","volume":"32","author":"Hardefeldt LY","year":"2020","unstructured":"Hardefeldt LY. 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