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Frontiers in veterinary science2022; 9; 1057667; doi: 10.3389/fvets.2022.1057667

Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis.

Abstract: Equine osteoarthritis (OA) is a heterogeneous, degenerative disease of the musculoskeletal system with multifactorial causation, characterized by a joint metabolic imbalance. Extracellular vesicles are nanoparticles involved in intracellular communication. Mesenchymal stem cell (MSC) therapy is a form of regenerative medicine that utilizes their properties to repair damaged tissues. Despite its wide use in veterinary practice, the exact mechanism of action of MSCs is not fully understood. The aim of this study was to determine the synovial fluid extracellular vesicle protein cargo following integrin α10β1-selected mesenchymal stem cell (integrin α10-MSC) treatment in an experimental model of equine osteoarthritis with longitudinal sampling. Unassigned: Adipose tissue derived, integrin α10-MSCs were injected intraarticularly in six horses 18 days after experimental induction of OA. Synovial fluid samples were collected at day 0, 18, 21, 28, 35, and 70. Synovial fluid was processed and extracellular vesicles were isolated and characterized. Extracellular vesicle cargo was then analyzed using data independent acquisition mass spectrometry proteomics. Unassigned: A total of 442 proteins were identified across all samples, with 48 proteins differentially expressed (FDR ≤ 0.05) between sham-operated control joint without MSC treatment and OA joint treated with MSCs. The most significant pathways following functional enrichment analysis of the differentially abundant protein dataset were serine endopeptidase activity (p = 0.023), complement activation (classical pathway) (p = 0.023), and collagen containing extracellular matrix (p = 0.034). Due to the lack of an OA group without MSC treatment, findings cannot be directly correlated to only MSCs. Unassigned: To date this is the first study to quantify the global extracellular vesicle proteome in synovial fluid following MSC treatment of osteoarthritis. Changes in the proteome of the synovial fluid-derived EVs following MSC injection suggest EVs may play a role in mediating the effect of cell therapy through altered joint homeostasis. This is an important step toward understanding the potential therapeutic mechanisms of MSC therapy, ultimately enabling the improvement of therapeutic efficacy.
Copyright © 2022 Clarke, Johnson, Caamaño Gutierrez, Andersen, Berg, Jenkins, Lindegaard, Uvebrant, Lundgren-Åkerlund, Turlo, James, Jacobsen and Peffers.
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Publication Date: 2022-11-24 PubMed ID: 36504839PubMed Central: PMC9730043DOI: 10.3389/fvets.2022.1057667Google 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 research article investigates the changes in synovial fluid proteins after treatment with specific types of stem cells in horses with osteoarthritis. The study aims to better understand how stem cell therapy works in treating degenerative joint diseases.

Objective and Methodology

  • The research aimed to analyze the proteins found in the extracellular vesicles (tiny particles emitted by cells) present in the synovial fluid (fluid found in joints) of horses suffering from osteoarthritis. The subjects were treated with mesenchymal stem cells (MSCs) that had been specifically selected for the presence of integrin α10β1, a type of protein.
  • MSC therapy, a form of regenerative medicine, was chosen because of its ability to repair damaged tissues — a crucial factor in the treatment of osteoarthritis. The study aimed to contribute to a better understanding of the precise mechanisms through which MSCs act.
  • The researchers caused experimental osteoarthritis in six horses and then treated them by injecting MSCs straight into the affected joints. Samples of synovial fluid were collected from the horses on various days throughout the study.
  • The collected fluid was processed, the extracellular vesicles were isolated and their protein content was analyzed using a specific type of protein study known as data independent acquisition mass spectrometry proteomics.

Findings and Interpretation

  • The researchers identified a total of 442 proteins in the synovial fluid samples. Forty-eight of these proteins were differentially expressed, meaning that there was a significant difference in the presence (expression) of these proteins between the osteoarthritic joints treated with MSCs and untreated control joints.
  • The proteins that were most significantly altered were involved in biological pathways related to enzyme activity, immune response, and the extracellular matrix, which provides structural and biochemical support to cells.
  • The changes in protein expression suggest that extracellular vesicles may play a key role in how stem cell therapy works. However, because all the osteoarthritic joints in the study were treated with MSCs, it is impossible to say whether these changes were due solely to the stem cell treatment.

Conclusions and Implications

  • This study suggests that the protein content of extracellular vesicles in joint fluid changes after MSC therapy. Understanding these changes could shed light on how stem cell treatments work to mitigate joint damage in osteoarthritis.
  • While this research provides new insights, the scientists highlight that further investigation is required. A comprehensive understanding of MSC therapy mechanisms will lead to enhancing the therapeutic effectiveness in the treatment of osteoarthritis.

Cite This Article

APA
Clarke EJ, Johnson E, Caamaño Gutierrez E, Andersen C, Berg LC, Jenkins RE, Lindegaard C, Uvebrant K, Lundgren-Åkerlund E, Turlo A, James V, Jacobsen S, Peffers MJ. (2022). Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis. Front Vet Sci, 9, 1057667. https://doi.org/10.3389/fvets.2022.1057667

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 9
Pages: 1057667

Researcher Affiliations

Clarke, Emily J
  • Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
Johnson, Emily
  • Computational Biology Facility, Liverpool Shared Research Facilities, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.
Caamaño Gutierrez, Eva
  • Computational Biology Facility, Liverpool Shared Research Facilities, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.
Andersen, Camilla
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Berg, Lise C
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jenkins, Rosalind E
  • Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, Centre for Drug Safety Science Bioanalytical Facility, Liverpool Shared Research Facilities, University of Liverpool, Liverpool, United Kingdom.
Lindegaard, Casper
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Uvebrant, Kristina
  • Xintela AB, Lund, Sweden.
Lundgren-Åkerlund, Evy
  • Xintela AB, Lund, Sweden.
Turlo, Agnieszka
  • Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
James, Victoria
  • School of Veterinary Medicine and Science, University of Nottingham, Nottingham, United Kingdom.
Jacobsen, Stine
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
Peffers, Mandy J
  • Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.

Grant Funding

  • MR/P020941/1 / Medical Research Council

Conflict of Interest Statement

Authors EL-Å and KU were employed by Xintela AB and have shares in the company. 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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