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Frontiers in veterinary science2022; 9; 907616; doi: 10.3389/fvets.2022.907616

Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation.

Abstract: Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in and small animal models and warrants further investigation. Unassigned: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Unassigned: Randomized positively and negatively controlled experimental study. Unassigned: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimulated allogeneic equine MSCs was injected in one randomly assigned joint, while the contralateral joint was injected with medium (negative control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded, and synovial fluid samples were analyzed for biomarkers (total protein, WBCC; eicosanoid mediators, CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed post-injection hours (PIH 0, 8, 24, 72, and 168 h). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time-treatment interactions were evaluated. For phase 2, allogeneic MSC-secretome vs. allogeneic equine MSCs (positive control) was tested using a similar methodology. Unassigned: In phase 1, the joint circumference was significantly ( < 0.05) lower in the MSC-secretome treated group compared to the medium control group at PIH 24, and significantly higher peak synovial GAG values were noted at PIH 24 ( < 0.001). In phase 2, no significant differences were noted between the treatment effects of MSC-secretome and MSCs. Unassigned: This study is a controlled experimental study and therefore cannot fully reflect natural joint disease. In phase 2, two therapeutics are directly compared and there is no negative control. Unassigned: In this model of joint inflammation, intra-articular MSC-secretome injection had some clinical anti-inflammatory effects. An effect on cartilage metabolism, evident as a rise in GAG levels was also noted, although it is unclear whether this could be considered a beneficial or detrimental effect. When directly comparing MSC-secretome to MSCs in this model results were comparable, indicating that MSC-secretome could be a viable off-the-shelf alternative to MSC treatment.
Copyright © 2022 Kearney, Khatab, van Buul, Plomp, Korthagen, Labberté, Goodrich, Kisiday, Van Weeren, van Osch and Brama.
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Publication Date: 2022-06-22 PubMed ID: 35812845PubMed Central: PMC9257274DOI: 10.3389/fvets.2022.907616Google Scholar: Lookup
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  • Journal Article

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 research article titled ‘Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation’ investigates the therapeutic effects of injecting mesenchymal stem cell (MSC) secretome into the joints of inflamed horse models.

Objective and Methodology

During the investigation, the goal was to determine whether the secretions of mesenchymal stem cells (MSCs) had an anti-inflammatory effect on equine joint inflammation. There were two phases in the study. In the first, inflammation was induced in the radiocarpal joints of eight horses by injecting lipopolysaccharide (LPS). Two hours later, one joint was randomly selected and treated with allogeneic equine MSCs’ secretome, while a medium was injected into the opposite joint as a negative control. The second phase involved comparing the anti-inflammatory effects of the MSCs’ secretome with that of allogeneic equine MSCs.

  • Clinical parameters including composite welfare scores, joint effusion, and joint circumference, were recorded.
  • Synovial fluid samples were analysed for the presence of various biomarkers at fixed intervals which were post-injection hours (PIH) 0, 8, 24, 72, and 168 hours.
  • The effects of time and treatment on metabolism and inflammation were studied and any time-treatment interactions were recorded.

Findings

During the first phase of the study, the researchers noticed a significant decrease in joint circumference in the group treated with MSC’s secretome compared to the control group. They also found an increase in synovial GAG values at PIH 24. In contrast, no marked differences in treatment effects between transmission of MSC-secretome and MSCs were discovered during the second phase.

Limitations

The primary limitations of the study were its controlled experimental nature, which can’t accurately mirror natural joint disease. Additionally, during the second phase, there was a direct comparison of two remedial interventions without a negative control.

Conclusion

The MSC-secretome injection appeared to have some anti-inflammatory effect on joint inflammation. This treatment also affected the joint’s cartilage metabolism, as indicated by a rise in synovial GAG levels. Nevertheless, the researchers are uncertain whether this could be considered a beneficial or detrimental effect. The results suggested that MSC-secretome could be a feasible substitute for MSC treatment as their effects on inflammation were comparable.

Cite This Article

APA
Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ. (2022). Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation. Front Vet Sci, 9, 907616. https://doi.org/10.3389/fvets.2022.907616

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 9
Pages: 907616
PII: 907616

Researcher Affiliations

Kearney, Clodagh M
  • School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
Khatab, Sohrab
  • Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
van Buul, Gerben M
  • Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
  • Beacon Hospital, Dublin, Ireland.
Plomp, Saskia G M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Korthagen, Nicoline M
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Labberté, Margot C
  • School of Veterinary Medicine, University College Dublin, Dublin, Ireland.
Goodrich, Laurie R
  • Equine Orthopaedic Research Center, Colorado State University, Fort Collins, CO, United States.
Kisiday, John D
  • Equine Orthopaedic Research Center, Colorado State University, Fort Collins, CO, United States.
Van Weeren, P R
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
van Osch, Gerjo J V M
  • Department of Orthopaedics and Sports Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
  • Department of Otorhinolaryngology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Brama, Pieter A J
  • School of Veterinary Medicine, University College Dublin, Dublin, Ireland.

Conflict of Interest Statement

The 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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