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Frontiers in veterinary science2022; 8; 789293; doi: 10.3389/fvets.2021.789293

Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries.

Abstract: The use of mesenchymal stem cells (MSCs) for the treatment of equine tendon disease is widely investigated because of their regenerative and immunomodulatory potential. However, questions have been raised concerning the immunogenic properties of allogeneic MSCs. Therefore, two studies were conducted to assess the safety of equine allogeneic peripheral blood-derived tenogenic primed MSCs (tpMSCs). The objective was to evaluate if a single and repeated tpMSC administration induced a cellular and humoral immune response in horses suffering from tendon injuries. Horses enrolled in the first study (n = 8) had a surgically induced superficial digital flexor tendon core lesion and were treated intralesionally with tpMSCs. Before and after treatment the cellular immunogenicity was assessed by modified mixed lymphocyte reactions. The humoral immune response was investigated using a crossmatch assay. Presence of anti-bovine serum albumin (BSA) antibodies was detected via ELISA. Horses enrolled in the second study (n = 6) suffered from a naturally occurring tendon injury and were treated twice with tpMSCs. Blood was collected after the second treatment for the same immunological assays. No cellular immune response was found in any of the horses. One out of eight horses in the first study and none of the horses in the second study had anti-tpMSC antibodies. This particular horse had an equine sarcoid and further investigation revealed presence of antibodies against sarcoid cells and epithelial-like stem cells before treatment, which increased after treatment. Additionally, formation of antibodies against BSA was observed. These findings might indicate a non-specific immune response generated after treatment. Serum from the other horses revealed no such antibody formation. These two studies showed that the administration of tpMSCs did not induce a cellular or humoral immune response following an intralesional single or repeated (two consecutive) allogeneic tpMSC treatment in horses with tendon injury, except for one horse. Therefore, a larger field study should confirm these findings and support the safe use of tpMSCs as a therapeutic for horses suffering from tendon injuries.
Copyright © 2022 Depuydt, Broeckx, Chiers, Patruno, Da Dalt, Duchateau, Saunders, Pille, Martens, Van Hecke and Spaas.
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Publication Date: 2022-02-24 PubMed ID: 35281431PubMed Central: PMC8907452DOI: 10.3389/fvets.2021.789293Google 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.

This research studies the safety of using mesenchymal stem cells (MSCs) for the treatment of tendon injuries in horses. In particular, it examines whether administering these stem cells at various intervals ignites an immune response in the horses.

Research Objectives and Methodology

  • The primary objective was to understand if the single and multiple introduction of tenogenic primed MSCs (tpMSCs), stem cells specialised for repairing tendons, would trigger an immune reaction in horses with tendon injuries.
  • To investigate this, two studies were conducted. In the first study, eight horses with surgically induced tendon injuries were treated with tpMSCs. In the second study, six horses with natural tendon wounds were treated twice with tpMSCs.
  • The researchers assessed the cellular immune reaction by studying lymphocyte reactions before and after treatment. The lymphocyte reaction helps illustrate how the body reacts to foreign entities. They also measured the humoral immune response using a crossmatch assay, which detects antibodies.
  • The presence of anti-bovine serum albumin (BSA) antibodies was observed through an enzyme lined immunosorbent assay (ELISA), a test that measures immune responses in the blood.

Research Findings

  • The research found no cellular immune response in any of the horses, indicating that the tpMSCs were not viewed as intruders by the horses’ bodies.
  • One horse among the first study group, and none in the second study group, developed antibodies against tpMSCs. Interestingly, the horse that did present antibodies had equine sarcoid, a common skin tumor in horses. Further testing revealed that this horse also developed increased antibodies against the cancer cells after treatment, suggesting a nonspecific immune response originating after therapy.
  • Some horses also showed antibody formation against BSA which is further evidence of a nonspecific immune response.
  • However, no such antibody formation was found in other horses’ serum.

Conclusions and Recommendations

  • Overall, the studies concluded that using tpMSCs to treat horses with tendon injuries didn’t provoke a cellular or humoral immune response after single or double application treatments.
  • The only exception was a horse with a pre-existing condition (equine sarcoid), and this requires further study.
  • The researchers recommend a larger field study to confirm these findings and ensure the safe use of tpMSCs for further application in treating horses with tendon injuries.

Cite This Article

APA
Depuydt E, Broeckx SY, Chiers K, Patruno M, Da Dalt L, Duchateau L, Saunders J, Pille F, Martens A, Van Hecke L, Spaas JH. (2022). Cellular and Humoral Immunogenicity Investigation of Single and Repeated Allogeneic Tenogenic Primed Mesenchymal Stem Cell Treatments in Horses Suffering From Tendon Injuries. Front Vet Sci, 8, 789293. https://doi.org/10.3389/fvets.2021.789293

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 8
Pages: 789293

Researcher Affiliations

Depuydt, Eva
  • Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Broeckx, Sarah Y
  • Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
Chiers, Koen
  • Department of Pathology, Bacteriology and Poultry Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Patruno, Marco
  • Department of Comparative Biomedicine and Food Science (BCA), University of Padova, Padova, Italy.
Da Dalt, Laura
  • Department of Comparative Biomedicine and Food Science (BCA), University of Padova, Padova, Italy.
Duchateau, Luc
  • Biometrics Research Group, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Saunders, Jimmy
  • 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.
Van Hecke, Lore
  • Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
Spaas, Jan H
  • Boehringer Ingelheim Veterinary Medicine Belgium, Evergem, Belgium.
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Conflict of Interest Statement

JHS declares competing financial interests as shareholder in Boehringer Ingelheim Veterinary Medicine Belgium (BIVMB) at the time of the study. SB, JHS, ED, and LV were all employed by BIVMB at the time of the study. The content of this manuscript contains a stem cell product under development (RenuTend®) owned and patented by BIVMB. 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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