Equine Fetal, Adult, and Embryonic Stem Cell-Derived Tenocytes Are All Immune Privileged but Exhibit Different Immune Suppressive Properties In Vitro.
Abstract: In horses and humans, tendon injuries are a significant problem. Not only can they occur in both athletes and nonathletes, they require lengthy periods of recuperation and undergo poor natural regeneration, which leads to high reinjury rates. Embryonic stem cells (ESCs) may provide a renewable source of allogeneic cells to use in clinical applications to aid tissue regeneration. Equine ESCs can undergo tenocyte differentiation in vivo and in vitro, but the immune properties of tenocytes isolated from either ESCs or tissues have not previously been characterized. Here, we demonstrate that equine tenocytes derived from fetal and adult tendon tissue and ESCs express robust levels of major histocompatibility complex (MHC) I but no MHC II in response to inflammatory cytokine interferon gamma (IFNγ). However, MHC expression does not affect their allorecognition by peripheral blood mononuclear cells in vitro. Adult and fetal tenocytes remain immune privileged and strongly immune suppressive in both the presence and absence of exogenously applied IFNγ. In contrast, ESC-derived tenocytes are immune privileged even in the presence of IFNγ, but they are only weakly immune suppressive in the presence but not in the absence of exogenously applied IFNγ. This is despite ESC-tenocytes expressing a number of genes involved in immune modulation at significantly higher levels than those expressed by adult and fetal tenocytes when in standard, nonstimulated monolayer culture. Together, this work suggests that, similar to other fibroblasts, tenocytes have immune modulatory properties, and that culture-expanded tenocytes derived from primary tissues or ESCs may be safe to use in clinical transplantations to injured tendons of unrelated animals.
Publication Date: 2019-10-08 PubMed ID: 31507234DOI: 10.1089/scd.2019.0120Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research examines the immune properties of cells derived from horse embryonic stem cells (ESCs) that could support tendon repair. The findings reveal these cells may be safe to use in transplants in unrelated injured animals due to their immune modulatory properties.
Background
- Tendon injuries are a significant problem in both humans and animals, particularly horses. The body’s natural regeneration process for tendons is often slow, leading to high reinjury rates.
- Embryonic stem cells (ESCs) may act as a potential allogeneic (taken from different individuals of the same species) cell source for treatment strategies intended for tissue regeneration.
- Equine ESCs can differentiate into tenocytes (tendon cells) both in living organisms (in vivo) and in a lab setting (in vitro), offering a possible solution for tendon repairs.
Research Findings
- This study marked the first time to categorically explore the immune properties of tenocytes derived from equine ESCs or tissues.
- The researchers found that tenocytes obtained from fetal and adult tendons, and ESCs, exhibited a strong expression of the major histocompatibility complex (MHC) I but not MHC II when treated with the inflammatory cytokine interferon gamma (IFNγ), a protein responsible for immune response regulation.
- Interestingly, the study revealed that while MHC expression is strong, it did not affect the allorecognition (recognition of one’s own cells by the immune system) by peripheral blood mononuclear cells in a lab setting.
- In terms of immune response, adult and fetal tenocytes proved to be immune privileged (not subject to immune response) and strongly immune suppressive regardless of the presence of exogenously applied IFNγ.
- Comparatively, tenocytes derived from ESCs retained their immune-privileged status even when exposed to IFNγ but only showed weak immune-suppressive properties when in contact with this cytokine, not when it is absent.
Conclusion
- This research demonstrates that tenocytes, similar to other fibroblasts (cells that make up connective tissues), possess immune modulatory properties, suggesting they could possibly play a part in managing the immune response.
- The study concluded with the suggestion that the use of tenocytes derived from both ESCs and primary tissues in clinical transplantations carried out on unrelated animals could be safe given their immune properties.
Cite This Article
APA
McClellan A, Paterson YZ, Paillot R, Guest DJ.
(2019).
Equine Fetal, Adult, and Embryonic Stem Cell-Derived Tenocytes Are All Immune Privileged but Exhibit Different Immune Suppressive Properties In Vitro.
Stem Cells Dev, 28(21), 1413-1423.
https://doi.org/10.1089/scd.2019.0120 Publication
Researcher Affiliations
- Centre for Preventive Medicine, Animal Health Trust, Newmarket, United Kingdom.
- Centre for Preventive Medicine, Animal Health Trust, Newmarket, United Kingdom.
- Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
- LABÉO Frank Duncombe, Caen, France.
- Normandie University, UniCaen, Biotargen, Saint-Contest, France.
- Centre for Preventive Medicine, Animal Health Trust, Newmarket, United Kingdom.
MeSH Terms
- Animals
- Cell Differentiation / physiology
- Cell Line
- Cell- and Tissue-Based Therapy / methods
- Embryonic Stem Cells / cytology
- Guided Tissue Regeneration / methods
- Histocompatibility Antigens Class I / immunology
- Horses
- Humans
- Immunomodulation / immunology
- Interferon-gamma / metabolism
- Interferon-gamma / pharmacology
- Leukocytes, Mononuclear / immunology
- Membrane Proteins / metabolism
- Tendon Injuries / therapy
- Tendons / cytology
- Tenocytes / cytology
- Tenocytes / immunology
- Tenocytes / transplantation
Citations
This article has been cited 4 times.- Smith EJ, Beaumont RE, McClellan A, Sze C, Palomino Lago E, Hazelgrove L, Dudhia J, Smith RKW, Guest DJ. Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors.. Cell Tissue Res 2023 Mar;391(3):523-544.
- Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases.. Animals (Basel) 2021 Jan 19;11(1).
- Im GI, Kim TK. Stem Cells for the Regeneration of Tendon and Ligament: A Perspective.. Int J Stem Cells 2020 Nov 30;13(3):335-341.
- Paterson YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ. Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes.. Stem Cell Res Ther 2020 May 19;11(1):184.
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