Antigenicity of mesenchymal stem cells in an inflamed joint environment.
Abstract: OBJECTIVE To determine whether major histocompatability complex (MHC) class II expression in equine mesenchymal stem cells (MSCs) changes with exposure to a proinflammatory environment reflective of an inflamed joint. SAMPLE Cryopreserved bone marrow-derived MSCs from 12 horses and cartilage and synovium samples from 1 horse euthanized for reasons other than lameness. PROCEDURES In part 1 of a 3-part study, the suitability of a quantitative reverse transcriptase PCR (qRT-PCR) assay for measurement of MHC class II expression in MSCs following stimulation with interferon (IFN)-γ was assessed. In part 2, synoviocyte-cartilage cocultures were or were not stimulated with interleukin (IL)-1β (10 ng/mL) to generate conditioned media that did and did not (control) mimic an inflamed joint environment. In part 3, a qRT-PCR assay was used to measure MSC MHC class II expression after 96 hours of incubation with 1 of 6 treatments (control-conditioned medium, IL-1β-conditioned medium, and MSC medium alone [untreated control] or with IL-1β [10 ng/mL], tumor necrosis factor-α [10 ng/mL], or IFN-γ [100 ng/mL]). RESULTS The qRT-PCR assay accurately measured MHC class II expression. Compared with MHC class II expression for MSCs exposed to the untreated control medium, that for MSCs exposed to IL-1β was decreased, whereas that for MSCs exposed to IFN-γ was increased. Neither the control-conditioned nor tumor necrosis factor-α medium altered MHC class II expression. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSC exposure to proinflammatory cytokine IL-1β decreased MHC class II expression and antigenicity. Treatment of inflamed joints with allogeneic MSCs might not be contraindicated, but further investigation is warranted.
Publication Date: 2017-06-27 PubMed ID: 28650243DOI: 10.2460/ajvr.78.7.867Google Scholar: Lookup
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- Evaluation Study
- Journal Article
Summary
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The study investigates how exposure to an inflamed joint environment affects the expression of major histocompatability complex (MHC) class II in horse mesenchymal stem cells (MSCs) and thus their antigenic properties which have implications for the treatment of inflamed joints.
Research Objective
- The main objective of the study was to investigate if the MHC class II expression in equine MSCs changed when exposed to an environment simulating an inflamed joint.
Sample Used
- The study used cryopreserved bone marrow-derived MSCs from 12 horses and cartilage and synovium samples from a horse euthanized for reasons not related to lameness.
Procedures
- This was a three-part study, with the first part involving the suitability assessment of a quantitative reverse transcriptase PCR (qRT-PCR) assay for measuring changes in MSC MHC class II expression in response to stimulation with interferon (IFN)-γ.
- The second part examined if synoviocyte-cartilage co-cultures were stimulated with interleukin (IL)-1β to create conditioned media that either mimicked an inflamed joint environment or not.
- The final part involved using the qRT-PCR assay to measure MHC class II expression in MSCs following a 96-hour exposure to one of six treatments (control-conditioned medium, IL-1β-conditioned medium, and MSC medium alone or with IL-1β, tumor necrosis factor-α, or IFN-γ).
Results
- The qRT-PCR assay was found to measure MHC class II expression accurately.
- MHC class II expression decreased in MSCs exposed to IL-1β but increased in MSCs exposed to IFN-γ compared to MSCs exposed to the untreated control medium. MHC class II expression was not altered by exposure to the control-conditioned medium or the tumor necrosis factor-α medium.
Conclusions and Clinical Relevance
- The results suggest that the exposure of MSCs to proinflammatory cytokine IL-1β decreases MHC class II expression and antigenicity. This suggests that potential treatment of inflamed joints with allogeneic MSCs may not be contraindicated, although further investigation is needed.
Cite This Article
APA
Hill JA, Cassano JM, Goodale MB, Fortier LA.
(2017).
Antigenicity of mesenchymal stem cells in an inflamed joint environment.
Am J Vet Res, 78(7), 867-875.
https://doi.org/10.2460/ajvr.78.7.867 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Culture Media, Conditioned
- Cytokines / metabolism
- Histocompatibility Antigens Class II / biosynthesis
- Histocompatibility Antigens Class II / immunology
- Horse Diseases / immunology
- Horses
- Inflammation / immunology
- Inflammation / veterinary
- Interleukin-1beta / metabolism
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / immunology
- Osteoarthritis / immunology
- Osteoarthritis / veterinary
- Real-Time Polymerase Chain Reaction / veterinary
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 12 times.- Jammes M, Contentin R, Cassé F, Galéra P. Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies.. Front Vet Sci 2023;10:1115774.
- Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ. Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation.. Front Vet Sci 2022;9:907616.
- Kamm JL, Riley CB, Parlane NA, Gee EK, McIlwraith CW. Immune response to allogeneic equine mesenchymal stromal cells.. Stem Cell Res Ther 2021 Nov 12;12(1):570.
- Harman RM, Marx C, Van de Walle GR. Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy.. Front Cell Dev Biol 2021;9:654885.
- Kamm JL, Riley CB, Parlane N, Gee EK, McIlwraith CW. Interactions Between Allogeneic Mesenchymal Stromal Cells and the Recipient Immune System: A Comparative Review With Relevance to Equine Outcomes.. Front Vet Sci 2020;7:617647.
- Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
- Lange-Consiglio A, Romele P, Magatti M, Silini A, Idda A, Martino NA, Cremonesi F, Parolini O. Priming with inflammatory cytokines is not a prerequisite to increase immune-suppressive effects and responsiveness of equine amniotic mesenchymal stromal cells.. Stem Cell Res Ther 2020 Mar 4;11(1):99.
- MacDonald ES, Barrett JG. The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in Horses.. Front Vet Sci 2019;6:507.
- Berthelot JM, Le Goff B, Maugars Y. Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylosing spondylitis: problems rather than solutions?. Arthritis Res Ther 2019 Nov 13;21(1):239.
- Bertoni L, Branly T, Jacquet S, Desancé M, Desquilbet L, Rivory P, Hartmann DJ, Denoix JM, Audigié F, Galéra P, Demoor M. Intra-Articular Injection of 2 Different Dosages of Autologous and Allogeneic Bone Marrow- and Umbilical Cord-Derived Mesenchymal Stem Cells Triggers a Variable Inflammatory Response of the Fetlock Joint on 12 Sound Experimental Horses.. Stem Cells Int 2019;2019:9431894.
- Broeckx SY, Seys B, Suls M, Vandenberghe A, Mariën T, Adriaensen E, Declercq J, Van Hecke L, Braun G, Hellmann K, Spaas JH. Equine Allogeneic Chondrogenic Induced Mesenchymal Stem Cells Are an Effective Treatment for Degenerative Joint Disease in Horses.. Stem Cells Dev 2019 Mar 15;28(6):410-422.
- Bogers SH. Cell-Based Therapies for Joint Disease in Veterinary Medicine: What We Have Learned and What We Need to Know.. Front Vet Sci 2018;5:70.
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