Equine Embryonic Stem Cell-Derived Tenocytes are Insensitive to a Combination of Inflammatory Cytokines and Have Distinct Molecular Responses Compared to Primary Tenocytes.
Abstract: Tissue fibrosis following tendon injury is a major clinical problem due to the increased risk of re-injury and limited treatment options; however, its mechanism remains unclear. Evidence suggests that insufficient resolution of inflammation contributes to fibrotic healing by disrupting tenocyte activity, with the NF-κB pathway being identified as a potential mediator. Equine embryonic stem cell (ESC) derived tenocytes may offer a potential cell-based therapy to improve tendon regeneration, but how they respond to an inflammatory environment is largely unknown. Our findings reveal for the first time that, unlike adult tenocytes, ESC-tenocytes are unaffected by IFN-γ, TNFα, and IL-1β stimulation; producing minimal changes to tendon-associated gene expression and generating 3-D collagen gel constructs indistinguishable from unstimulated controls. Inflammatory pathway analysis found these inflammatory cytokines failed to activate NF-κB in the ESC-tenocytes. However, NF-κB could be activated to induce changes in gene expression following stimulation with NF-κB pharmaceutical activators. Transcriptomic analysis revealed differences between cytokine and NF-κB signalling components between adult and ESC-tenocytes, which may contribute to the mechanism by which ESC-tenocytes escape inflammatory stimuli. Further investigation of these molecular mechanisms will help guide novel therapies to reduce fibrosis and encourage superior tendon healing.
© 2024. The Author(s).
Publication Date: 2024-02-24 PubMed ID: 38396222PubMed Central: 4195467DOI: 10.1007/s12015-024-10693-8Google Scholar: Lookup
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- Journal Article
Summary
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The research article explores how tenocytes, a type of cell found in tendons, derived from equine or horse embryonic stem cells behave in inflammatory conditions. It was found that these stem cell-derived tenocytes, unlike adult tenocytes, do not respond to inflammation due to certain genes and produce minimal changes.
Background
- This research targets the challenge of tissue fibrosis after a tendon injury, which poses a risk as it leads to re-injury and there are limited treatment options available. The mechanisms of fibrosis aren’t well understood.
- This study works on the hypothesis that insufficient resolution of inflammation contributes to fibrotic healing and disturbs tenocyte activity.
- It recognizes the NF-κB pathway as a potential mediator in the process.
Research Aim
- The research was designed to explore equine embryonic stem cell (ESC) derived tenocytes’ response to inflammation, as these can potentially be used to improve tendon regeneration.
Research Findings
- The research found that ESC-derived tenocytes, unlike adult tenocytes, are not affected by inflammatory cytokines IFN-γ, TNFα, and IL-1β.
- They produced minimal changes in tendon-associated gene expression after stimulation with these cytokines.
- They also produced 3-D collagen gel constructs equivalent to unstimulated controls.
- The pathway analysis revealed that these inflammatory cytokines did not activate the NF-κB pathway in ESC-tenocytes, which is a new finding in this field.
- However, it was found that this pathway could be activated using pharmaceutical activators.
Transcriptomic Analysis
- A deeper analysis of genes showed differences between adult tenocytes and ESC-derived tenocytes with respect to cytokine and NF-κB signalling components.
- These differences may explain why ESC-derived tenocytes are unaffected by inflammatory stimuli.
Summary
- This research adds to our understanding of how tenocytes respond to inflammation and further exploration of these mechanisms can lead to novel therapies aimed to decrease fibrosis and improve tendon healing.
Cite This Article
APA
Smith EJ, Beaumont RE, Dudhia J, Guest DJ.
(2024).
Equine Embryonic Stem Cell-Derived Tenocytes are Insensitive to a Combination of Inflammatory Cytokines and Have Distinct Molecular Responses Compared to Primary Tenocytes.
Stem Cell Rev Rep.
https://doi.org/10.1007/s12015-024-10693-8 Publication
Researcher Affiliations
- Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK. ejsmith@rvc.ac.uk.
- Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
- Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK.
- Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, UK. djguest@rvc.ac.uk.
Grant Funding
- VET/RS/257 / Horserace Betting Levy Board
- S19-747- 786 / Petplan Charitable Trust
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