Revealing the Therapeutic Potential of Muscle-Derived Mesenchymal Stem/Stromal Cells: An In Vitro Model for Equine Laminitis Based on Activated Neutrophils, Anoxia-Reoxygenation, and Myeloperoxidase.
Abstract: Laminitis in horses is a crippling condition marked by the deterioration of the dermal-epidermal interface, leading to intense lameness and discomfort, often necessitating euthanasia. This study aimed to establish an in vitro model of laminitis using a continuous keratinocyte cell line exposed to anoxia-reoxygenation and an activated neutrophil supernatant. A significant decrease in the keratinocytes' metabolism was noted during the reoxygenation period, indicative of cellular stress. Adding muscle-derived mesenchymal stem/stromal cells during the reoxygenation demonstrated a protective effect, restoring the keratinocytes' metabolic activity. Moreover, the incubation of the keratinocytes with either an activated neutrophil supernatant or myeloperoxidase alone induced increased keratinocyte myeloperoxidase activity, which was modulated by stem cells. These findings underscore the potential of muscle-derived mesenchymal stem/stromal cells in mitigating inflammation and restoring keratinocyte metabolism, offering insights for future cell therapy research in laminitis treatment.
Publication Date: 2024-09-14 PubMed ID: 39335269PubMed Central: PMC11428732DOI: 10.3390/ani14182681Google Scholar: Lookup
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- Journal Article
Summary
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The research article describes an experiment to investigate the use of muscle-derived mesenchymal stem/stromal cells (MDMSCs) as a potential treatment for laminitis – a painful disease affecting horses. The scientists discovered that these cells can reduce inflammation and restore cell metabolism, hinting at their potential application in future therapies for this condition.
Objective and Methods of the Study
- The study was conducted to examine the therapeutic potential of MDMSCs in treating laminitis in horses, a crippling condition often leading to euthanasia.
- The researchers developed an in-vitro model. In this model, keratinocyte cells (which make up a substantial part of the dermal-epidermal junction) were exposed to anoxia-reoxygenation and activated neutrophil supernatant – conditions that mimic the environment during a laminitis episode.
Findings on Keratinocyte Metabolism
- The scientists observed a significant decrease in the metabolism of the keratinocyte cells during the reoxygenation period, reflecting a state of cellular stress analogous to what occurs during a laminitis attack.
- When MDMSCs were added during reoxygenation, they had a protective effect, restoring the metabolic activity of the keratinocytes.
Impact of Activated Neutrophil Supernatant and Myeloperoxidase
- The researchers also noticed an increase in keratinocyte’s myeloperoxidase (MPO) activity when they were incubated with either activated neutrophil supernatant or MPO alone. MPO is an enzyme found in neutrophils and it’s been associated with inflammatory conditions. This suggests that these elements contribute to the inflammation seen in laminitis.
- However, this increased MPO activity was reduced when MDMSCs were present, showing the stem cells’ ability to mitigate inflammation.
Implications for Laminitis Treatment
- These findings highlight the potential for MDMSCs in reducing inflammation and restoring cell metabolism under stress conditions – which are crucial features needed for a laminitis treatment.
- The study provides a valuable foundation for future research into cell therapy options for managing and treating laminitis in horses.
Cite This Article
APA
Serteyn D, Storms N, Mouithys-Mickalad A, Sandersen C, Niesten A, Duysens J, Graide H, Ceusters J, Franck T.
(2024).
Revealing the Therapeutic Potential of Muscle-Derived Mesenchymal Stem/Stromal Cells: An In Vitro Model for Equine Laminitis Based on Activated Neutrophils, Anoxia-Reoxygenation, and Myeloperoxidase.
Animals (Basel), 14(18).
https://doi.org/10.3390/ani14182681 Publication
Researcher Affiliations
- Department of Equine Clinical Sciences, University of Liège, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Department of Equine Clinical Sciences, University of Liège, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Department of Equine Clinical Sciences, University of Liège, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
- Center for Oxygen Research and Development, B6, University of Liège, FARAH, Quartier Vallée 2 Avenue de Cureghem 5D, 4000 Liège, Belgium.
Grant Funding
- Mitotrans / French Community of Belgium
Conflict of Interest Statement
D. Serteyn and J. Ceusters are the co-inventors of a patent related to muscle-derived stem cells. This patent is licensed by the University of Liège to Revatis, a spin-off company in which D. Serteyn and J. Ceusters serve as scientific advisors. The other co-authors declare no conflicts of interest.
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