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.
Abstract: To investigate mechanistically the reported beneficial effects of immune-activated mesenchymal stromal cell (MSC) therapy to treat equine septic arthritis, leveraging Nanostring technology. Methods: 8 Quarter Horses with induced tibiotarsal Staphylococcus aureus septic arthritis treated IA with either Toll-like receptor-3 agonist polyinosinic:polycytidylic acid-activated MSCs + vancomycin antimicrobials (TLR-MSC-VAN; n = 4) or antimicrobials (VAN; 4). Methods: 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- versus VAN-treated joints. Results: 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 ≥ 2 or ≤ -2 and a significant false discovery rate-adjusted P value of ≤ .05. The most upregulated genes in TLR-MSC-VAN-treated 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-treated horses, which did not reach statistical significance in this small sample set (P = .20). Conclusions: 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.
Publication Date: 2024-02-03 PubMed ID: 38295517DOI: 10.2460/javma.23.10.0561Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The given research article explores the beneficial impact of immune-activated mesenchymal stromal cell (MSC) therapy on horses suffering from septic arthritis, using Nanostring technology to observe T-cell response pathways within synovial tissues.
Objective and Methodology
- The objective of the study was to understand the mechanism behind the benefits of immune-activated mesenchymal stromal cell (MSC) therapy in treating equine septic arthritis. The researchers adopted an advanced biotechnology, Nanostring, which allows for targeted transcriptomic analysis.
- The animal subjects were 8 Quarter Horses, induced with tibiotarsal Staphylococcus aureus septic arthritis. They were treated via intra-articular (IA) processes with either a combination of Toll-like receptor-3 agonist polyinosinic: polycytidylic acid-activated MSCs and vancomycin antimicrobials (TLR-MSC-VAN) or just antimicrobials (VAN).
- Synovial tissues of the horses were collected and genetically sequenced using an equine Nanostring nCounter immune panel, which allowed for direct quantification of immune and cartilage-related genes. This signified the core part of the analysis.
Findings
- Transcriptomic comparison between the groups showed moderate changes in gene expression, with 9 genes considerably upregulated and 17 downregulated, indicating a nuanced alteration in their immune response due to different treatment methods.
- The TLR-MSC-VAN technique led to significantly increased expression of genes related to T-lymphocyte function and recruitment, symbolizing a superior adaptive immune response. Counteractively, the genes related to innate immune activation and inflammation were evidently downregulated, which signals a reduction in inflammatory immune response.
- The team performed Immunohistochemistry, a process for detecting specific proteins in cells of a tissue section, to quantify T-cell infiltration. They found a comparatively higher infiltrate in the synovial tissues of TLR-MSC-VAN-treated horses.
- The numerical superiority of T-cell infiltrate in TLR-MSC-VAN-treated samples, however, was statistically insignificant due to the small size of the study group.
Conclusion
- A targeted transcriptomic analysis using equine Nanostring immune and cartilage health panel provided deep insights into the unique immunological response within synovial tissues when subjected to the TLR-activated MSC treatment.
- However, the study found that the elevated T-cell response in the TLR-activated MSC treatment group was not significantly different from the antimicrobial-only group due to a small sample size, suggesting the necessity of further research with broader studies.
Cite This Article
APA
Pezzanite LM, Chow L, Engiles JB, Kurihara J, Plaisance C, Goodrich LR, Dow S.
(2024).
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.
J Am Vet Med Assoc, 1-10.
https://doi.org/10.2460/javma.23.10.0561 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Departments of Pathobiology and Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.