Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon.
Abstract: Tendon injuries are a common problem in humans and horses. There is a high re-injury rate in both species due to the poor regeneration of adult tendon and the resulting formation of scar tissue. In contrast, fetal tendon injuries undergo scarless regeneration, but the mechanisms which underpin this are poorly defined. It is also unclear if tendon cells derived from embryonic stem cells (ESCs) would aid tendon regeneration. In this study we determined the responses of adult, fetal and ESC-derived equine tenocytes to a range of cytokines, chemokines and growth factors that are upregulated following a tendon injury using both 2-dimensional (2D) and 3-dimensional (3D) in vitro wound models. We demonstrated that in 2D proliferation assays, the responses of fetal and adult tenocytes to the factors tested are more similar to each other than to ESC-tenocytes. However, in 2D migration assays, fetal tenocytes have similarities to both adult and ESC-tenocytes. In 3D wound closure assays the response of fetal tenocytes also appears to be intermediary between adult and ESC-tenocytes. We further demonstrated that while TGFβ3 increases 3D gel contraction and wound healing by adult and fetal tenocytes, FGF2 results in a significant inhibition by adult cells. In conclusion, our findings suggest that differential cellular responses to the factors upregulated following a tendon injury may be involved in determining if tendon repair or regeneration subsequently occurs. Understanding the mechanisms behind these responses is required to inform the development of cell-based therapies to improve tendon regeneration.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Publication Date: 2025-02-08 PubMed ID: 39929423DOI: 10.1016/j.cdev.2025.204003Google Scholar: Lookup
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- Journal Article
Summary
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The research article focuses on how adult, fetal, and embryonic stem cell-derived tenocytes (tendon cells) from horses respond differently to various factors that increase after a tendon injury. Using 2-dimensional and 3-dimensional models, the study examines cellular reaction to these factors to understand their role in either repairing or regenerating the tendon. This understanding could then inform the development of cell-based therapies for improved tendon healing and regeneration.
Investigation of Tendon Cells Response to Injury Factors
- The study involved determining the reactions of adult, fetal, and embryonic stem cell (ESC)-derived tenocytes from horses to different factors (cytokines, chemokines, and growth factors) that increase after a tendon injury.
- This was achieved through 2-dimensional (2D) and 3-dimensional (3D) in vitro wound models, which simulated the environment and conditions of a real injury.
Proliferation and Migration in 2D Models
- Using 2D proliferation assays, the study demonstrated that the reactions of fetal and adult tenocytes to the tested factors were more similar to each other and drastically different from the reactions of embryonic stem cell-derived tenocytes.
- However, 2D migration assays suggested a certain level of similarity between fetal, adult, and ESC-derived tenocytes in terms of movement and spread in response to injury factors.
Response in 3D Wound Closure Assays
- In 3D wound closure assays also, the response of fetal tenocytes appeared to be intermediary, demonstrating characteristics between adult and embryonic stem cell-derived tenocytes.
- The study further showed that TGFβ3, one of the studied factors, enhances 3D gel contraction and wound healing in adult and fetal tenocytes, while FGF2 inhibits these processes in adult cells.
Implications of the Research
- The findings from this research suggest that the difference in cellular responses to the upregulated factors following a tendon injury may determine whether the tendon gets repaired or regenerated.
- The observed differential response of tenocytes thus needs further investigation and understanding, as it can inform the development of cell-based therapies for tendon regeneration, potentially improving the treatment and prognosis of tendon injuries in both horses and humans.
Cite This Article
APA
Beaumont RE, Smith EJ, David C, Paterson YZ, Faull E, Guest DJ.
(2025).
Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon.
Cells Dev, 181, 204003.
https://doi.org/10.1016/j.cdev.2025.204003 Publication
Researcher Affiliations
- Centre for Vaccinology and Regenerative Medicine, Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK.
- Centre for Vaccinology and Regenerative Medicine, Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK.
- Centre for Vaccinology and Regenerative Medicine, Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK; UFR Sciences, Aix-Marseille University, 163 Av. de Luminy, 13009 Marseille, France.
- Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Newmarket, Suffolk CB8 7UU, UK; Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
- Centre for Vaccinology and Regenerative Medicine, Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK.
- Centre for Vaccinology and Regenerative Medicine, Department of Clinical Sciences and Services, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK. Electronic address: djguest@rvc.ac.uk.
MeSH Terms
- Horses
- Animals
- Tenocytes / metabolism
- Tenocytes / drug effects
- Tenocytes / cytology
- Tenocytes / pathology
- Tendon Injuries / pathology
- Tendon Injuries / genetics
- Tendon Injuries / metabolism
- Cell Movement / drug effects
- Cell Movement / genetics
- Cell Proliferation / drug effects
- Up-Regulation / drug effects
- Embryonic Stem Cells / cytology
- Embryonic Stem Cells / metabolism
- Embryonic Stem Cells / drug effects
- Fetus / cytology
- Wound Healing / drug effects
- Tendons / pathology
- Fibroblast Growth Factor 2 / pharmacology
- Cytokines / pharmacology
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