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Frontiers in veterinary science2021; 8; 641441; doi: 10.3389/fvets.2021.641441

The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model.

Abstract: Tendon injuries are very common in horses and jeopardize the athletic performance, and due to the high risk of reinjury may lead to early retirement. The use of mesenchymal stem cells for the treatment of equine tendon disease is widely investigated because of their regenerative potential. The objective of this study is to investigate the safety and efficacy of equine allogeneic tenogenic primed mesenchymal stem cells (tpMSCs) for the management of tendinitis in horses. A core lesion was surgically induced in the superficial digital flexor tendon of both forelimbs of eight horses. After 7 days, one forelimb was treated with tpMSCs, while the contralateral forelimb served as an intra-individual control and was treated with saline. A prescribed exercise program was started. All horses underwent a daily clinical evaluation throughout the entire study period of 112 days. Blood samples were taken at different time points for hematological and biochemical analysis. Tendon assessment, lameness examination, ultrasound assessment and ultrasound tissue characterization (UTC) were performed at regular time intervals. At the end of the study period, the superficial digital flexor tendons were evaluated macroscopically and histologically. No suspected or serious adverse events occurred during the entire study period. There was no difference in local effects including heat and pain to pressure between a single intralesional injection of allogeneic tpMSCs and a single intralesional injection with saline. A transient moderate local swelling was noted in the tpMSC treated limbs, which dissipated by day 11. Starting at a different time point depending on the parameter, a significant improvement was observed in the tpMSC treated limbs compared to the placebo for echogenicity score, fiber alignment score, anterior-posterior thickness of the tendon and echo type by UTC assessment. Immunohistochemistry 112 days post-injection revealed that the amount of collagen type I and Von Willebrand factor were significantly higher in the tendon tissue of the tpMSC group, while the amount of collagen type III and smooth muscle actin was significantly lower. Equine allogeneic tenogenic primed mesenchymal stem cells were shown to be well-tolerated and may be effective for the management of tendon injuries.
Copyright © 2021 Depuydt, Broeckx, Van Hecke, Chiers, Van Brantegem, van Schie, Beerts, Spaas, Pille and Martens.
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Publication Date: 2021-03-05 PubMed ID: 33748217PubMed Central: PMC7973085DOI: 10.3389/fvets.2021.641441Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the use of a type of stem cell, called tenogenic primed mesenchymal stem cells (tpMSCs), in treating tendon injuries in horses. Researchers found that the treatment led to significant improvements in different parameters associated with tendon healing and function, and was also well tolerated by the horses.

Study Methodology

  • The study involved creating a superficial digital flexor tendon injury in both forelimbs of eight horses. After a week, one forelimb of each horse was treated using tpMSCs, and the other forelimb treated with saline as a control.
  • The horses were then subjected to a prescribed exercise program, and clinically evaluated daily for a total study period of 112 days.
  • Blood samples were taken periodically for analysis. Various assessments, such as examination for lameness, tendon evaluation, and ultrasound, were performed at regular intervals. At the end of the study, the tendons were evaluated macroscopically and histologically.

Findings of the Study

  • No serious or suspected adverse effects were observed throughout the research period. There were no significant differences in pain levels or local heat effects between the limbs treated with tpMSCs and those treated with saline.
  • A transient, moderate swelling was noted in the limbs treated with tpMSCs, which subsided by the 11th day.
  • Starting from different periods, depending on the parameter being observed, the limbs treated with tpMSCs showed significant improvement in terms of echogenicity score, fiber alignment, thickness of the tendon, and echo type.
  • At 112 days post-injection, the tpMSC-treated tendons showed higher amounts of collagen type I and Von Willebrand factor, which are beneficial for healing, and lower amounts of collagen type III and smooth muscle actin, which are often correlated with scar formation and poorer healing. This suggested that tpMSC treatment might prompt a more successful, efficient healing process.

Implications of the Study

  • The study demonstrates that equine allogeneic tpMSCs are well-tolerated and might be effective in the management of tendon injuries. Hence, tpMSC therapy could potentially reduce the risk of reinjury and facilitate a faster return to athletic performance for horses suffering from tendon diseases.

Cite This Article

APA
Depuydt E, Broeckx SY, Van Hecke L, Chiers K, Van Brantegem L, van Schie H, Beerts C, Spaas JH, Pille F, Martens A. (2021). The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model. Front Vet Sci, 8, 641441. https://doi.org/10.3389/fvets.2021.641441

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 8
Pages: 641441
PII: 641441

Researcher Affiliations

Depuydt, Eva
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Broeckx, Sarah Y
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
Van Hecke, Lore
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
Chiers, Koen
  • Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Van Brantegem, Leen
  • Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
van Schie, Hans
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
  • Department of Research and Development, UTC Imaging, Stein, Netherlands.
Beerts, Charlotte
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Spaas, Jan H
  • Global Stem cell Technology, Part of Boehringer Ingelheim, Evergem, Belgium.
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Pille, Frederik
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Martens, Ann
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Conflict of Interest Statement

JS declares competing financial interests as shareholder in GST at the time of the study. SB, JS, ED, CB, and LH were all employed by GST at the time of the study. The content of this manuscript contains a stem cell product under development (Tendo-Cell® Plus) owned by GST and patented under the following numbers: EP13799605.4, CA2928122, US15/038,172. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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