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Frontiers in bioengineering and biotechnology2023; 11; 1204737; doi: 10.3389/fbioe.2023.1204737

Effect of pro-inflammatory cytokine priming and storage temperature of the mesenchymal stromal cell (MSC) secretome on equine articular chondrocytes.

Abstract: Osteoarthritis (OA) is an invalidating articular disease characterized by cartilage degradation and inflammatory events. In horses, OA is associated with up to 60% of lameness and leads to reduced animal welfare along with extensive economic losses; currently, there are no curative therapies to treat OA. The mesenchymal stromal cell (MSC) secretome exhibits anti-inflammatory properties, making it an attractive candidate for improving the management of OA. In this study, we determined the best storage conditions for conditioned media (CMs) and tested whether priming MSCs with cytokines can enhance the properties of the MSC secretome. First, properties of CMs collected from bone-marrow MSC cultures and stored at -80°C, -20°C, 4°C, 20°C or 37°C were assessed on 3D cultures of equine articular chondrocytes (eACs). Second, we primed MSCs with IL-1β, TNF-α or IFN-γ, and evaluated the MSC transcript levels of immunomodulatory effectors and growth factors. The primed CMs were also harvested for subsequent treatment of eACs, either cultured in monolayers or as 3D cell cultures. Finally, we evaluated the effect of CMs on the proliferation and the phenotype of eACs and the quality of the extracellular matrix of the neosynthesized cartilage. CM storage at -80°C, -20°C, and 4°C improved collagen protein accumulation, cell proliferation and the downregulation of inflammation. The three cytokines chosen for the MSC priming influenced MSC immunomodulator gene expression, although each cytokine led to a different pattern of MSC immunomodulation. The cytokine-primed CM had no major effect on eAC proliferation, with IL-1β and TNF-α slightly increasing collagen (types IIB and I) accumulation in eAC 3D cultures (particularly with the CM derived from MSCs primed with IL-1β), and IFN-γ leading to a marked decrease. IL-1β-primed CMs resulted in increased eAC transcript levels of and , whereas IFNγ-primed CMs decreased the levels of and . Although the three cytokines differentially affected the expression of immunomodulatory molecules, primed CMs induced a distinct effect on eACs according to the cytokine used for MSC priming. Different mechanisms seemed to be triggered by each priming cytokine, highlighting the need for further investigation. Nevertheless, this study demonstrates the potential of MSC-CMs for improving equine OA management.
Copyright © 2023 Jammes, Contentin, Audigié, Cassé and Galéra.
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Publication Date: 2023-08-31 PubMed ID: 37720315PubMed Central: PMC10502223DOI: 10.3389/fbioe.2023.1204737Google 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 focuses on understanding how the secretome from mesenchymal stromal cells (MSCs), when exposed to certain cytokines and stored at optimal conditions, could potentially improve the treatment of osteoarthritis in horses.

Significance of the Study

  • Osteoarthritis is a debilitating joint disease that often leads to cartilage damage and inflammation. In the equine world, it’s responsible for up to 60% of lameness, negatively impacting animal welfare and resulting in financial loss.
  • Currently, there are no curative therapies for osteoarthritis, making this research of significant importance.
  • The prime focus of this study is on the secretome of mesenchymal stromal cells (MSCs), which is known for its anti-inflammatory properties. Therefore, it shows promise in managing osteoarthritis.

Research Methodology

  • The study aimed to identify the best storage conditions for conditioned media (CMs) and to determine if ‘priming’ MSCs with cytokines could enhance the secretome’s properties.
  • To do this, CMs were collected from bone-marrow MSC cultures and stored at various temperatures. Then, these CMs were assessed on 3D cultures of equine articular chondrocytes (eACs).
  • The researchers also primed MSCs with IL-1β, TNF-α or IFN-γ. They then evaluated the MSC transcript levels, harvested the primed CMs, and used them to treat eACs in culture, either monolayered or 3D.
  • Finally, the researchers evaluated the CMs’ effect on eAC proliferation, phenotype, and the quality of the newly synthesized cartilage’s extracellular matrix.

Key Findings

  • The best storage conditions for the CMs were -80°C, -20°C, and 4°C, which improved collagen protein accumulation, cell proliferation and the downregulation of inflammation.
  • The specific cytokines used for MSC priming noticeably influenced MSC immunomodulator gene expression. However, each cytokine induced a different immunomodulation pattern in MSCs.
  • The cytokine-primed CMs did not majorly affect eAC proliferation. IL-1β and TNF-α slightly increased collagen accumulation in eAC 3D cultures, particularly with the CM from MSCs primed with IL-1β. Meanwhile, IFN-γ caused a significant decrease.
  • IL-1β-primed and IFNγ-primed CMs had different effects on eAC transcript levels, demonstrating distinct effects on eACs based on the cytokine used for MSC priming.

Conclusion and Implication

  • Although each priming cytokine triggered different immunomodulatory mechanisms, it’s clear that primed CMs could potentially become an efficient player in managing equine osteoarthritis.
  • The findings underline the importance of further research in this area to clarify the mechanisms triggered by each priming cytokine.

Cite This Article

APA
Jammes M, Contentin R, Audigié F, Cassé F, Galéra P. (2023). Effect of pro-inflammatory cytokine priming and storage temperature of the mesenchymal stromal cell (MSC) secretome on equine articular chondrocytes. Front Bioeng Biotechnol, 11, 1204737. https://doi.org/10.3389/fbioe.2023.1204737

Publication

Frontiers in bioengineering and biotechnology
ISSN: 2296-4185
NlmUniqueID: 101632513
Country: Switzerland
Language: English
Volume: 11
Pages: 1204737
PII: 1204737

Researcher Affiliations

Jammes, Manon
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.
Contentin, Romain
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.
Audigié, Fabrice
  • Unit Under Contract 957 Equine Biomechanics and Locomotor Disorders (USC 957 BPLC), Center of Imaging and Research on Locomotor Affections on Equines (CIRALE), French National Research Institute for Agriculture Food and Environment (INRAE), École Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
Cassé, Frédéric
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.
Galéra, Philippe
  • Normandie University, UNICAEN, BIOTARGEN, Caen, France.

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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