Pre-conditioning of Equine Bone Marrow-Derived Mesenchymal Stromal Cells Increases Their Immunomodulatory Capacity.
Abstract: Mesenchymal stem/stromal cells (MSCs) are increasingly explored for the treatment of degenerative and inflammatory diseases in human and veterinary medicine. One of the key characteristics of MSCs is that they modulate inflammation mainly through the secretion of soluble mediators. However, despite widespread clinical use, knowledge regarding the effector mechanisms of equine MSCs, and consequently their effectiveness in the treatment of diseases, is still unknown. The objectives of this study were to determine the mechanisms underlying inhibition of lymphocyte proliferation by equine bone marrow-derived MSCs, and to evaluate the effect of pre-conditioning of equine MSCs with different pro-inflammatory cytokines on inhibition of lymphocyte proliferation. We determined that inhibition of lymphocyte proliferation by equine MSCs depends on activity of prostaglandin-endoperoxide synthase 2 and indoleamine 2,3-dioxygenase. Additionally, pre-conditioning of MSCs with TNF-α, IFN-γ or their combination significantly increased the expression of prostaglandin-endoperoxide synthase 2, indoleamine 2,3-dioxygenase, iNOS and IL-6. This upregulation correlated with an increased inhibitory effect of MSCs on lymphocyte proliferation. In conclusion, pre-conditioning of bone marrow-derived MSC increases their inhibitory effect on lymphocyte proliferation in horses.
Copyright © 2020 Caffi, Espinosa, Gajardo, Morales, Durán, Uberti, Morán, Plaza and Henríquez.
Publication Date: 2020-06-11 PubMed ID: 32656251PubMed Central: PMC7325884DOI: 10.3389/fvets.2020.00318Google Scholar: Lookup
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- Journal Article
Summary
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This study focuses on improving the effectiveness of equine Mesenchymal Stem/Stromal Cells (MSCs) in modulating inflammatory responses. The researchers discovered that preconditioning MSCs with specific cytokines boosts their immunomodulatory capacity, thus enhancing their efficacy in inhibiting lymphocyte proliferation.
Mesenchymal Stem/Stromal Cells (MSCs) and Inflammation
- The study investigates the functionality of equine MSCs, which are cell types extensively studied for their potential role in treating degenerative and inflammatory diseases in both humans and animals.
- One of the main characteristics of MSCs is their ability to regulate inflammation, primarily through the secretion of soluble mediators.
- Despite their broad clinical use, researchers still have limited understanding of the exact mechanisms by which equine MSCs inhibit inflammatory responses, particularly lymphocyte proliferation — a fundamental process in the immune response.
Objectives of the Study
- The aim of this research was to identify and understand the mechanisms that underpin the inhibitory effect of equine bone marrow-derived MSCs on lymphocyte proliferation.
- Additionally, the researchers sought to examine how preconditioning MSCs with different pro-inflammatory cytokines impact their effectiveness in inhibiting lymphocyte proliferation.
Study Findings
- Researchers found that the inhibition of lymphocyte proliferation by equine MSCs deploys two main mechanisms: Prostaglandin-endoperoxide synthase 2 (PGHS-2) and indoleamine 2,3-dioxygenase (IDO).
- Furthermore, they discovered that preconditioning MSCs with Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN-γ) or a combination of both significantly enhances the expression of PGHS-2, IDO, inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6).
- This increased expression correlates with an enhanced capacity of MSCs to inhibit lymphocyte proliferation, suggesting that preconditioning can maximize the immunomodulatory properties of these cells.
Conclusion
- The study concludes that preconditioning bone marrow-derived MSCs enhances their inhibitory impact on lymphocyte proliferation in horses.
- These findings could have significant implications for the use of MSCs in therapeutic interventions targeting inflammatory and degenerative diseases in both veterinary and human medicine.
Cite This Article
APA
Caffi V, Espinosa G, Gajardo G, Morales N, Durán MC, Uberti B, Morán G, Plaza A, Henríquez C.
(2020).
Pre-conditioning of Equine Bone Marrow-Derived Mesenchymal Stromal Cells Increases Their Immunomodulatory Capacity.
Front Vet Sci, 7, 318.
https://doi.org/10.3389/fvets.2020.00318 Publication
Researcher Affiliations
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Escuela de Graduados, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Escuela de Graduados, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Escuela de Graduados, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Instituto de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Instituto de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
- Instituto de Medicina, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
- Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
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