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Frontiers in immunology2016; 7; 392; doi: 10.3389/fimmu.2016.00392

Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells.

Abstract: Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA. Methods: ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluated by histology and RT-qPCR. For functional assays, naïve or IFNγ-primed eASCs were cocultured with peripheral blood mononuclear cells or articular cartilage explants. Finally, the therapeutic effect of eASCs was tested in the model of collagenase-induced OA (CIOA) in mice. Results: The immunosuppressive function of eASCs on equine T cell proliferation and their chondroprotective effect on equine cartilage explants were demonstrated . Both cartilage degradation and T cell activation were reduced by naïve and IFNγ-primed eASCs, but IFNγ-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFNγ-primed eASCs were more potent than naïve cells. This effect was related to the modulation of eASC secretome by IFNγ-priming. Conclusions: IFNγ-priming of eASCs potentiated their antiproliferative and chondroprotective functions. We demonstrated that the immunocompetent mouse model of CIOA was relevant to test the therapeutic efficacy of xenogeneic eASCs for OA and confirmed that IFNγ-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine.
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Publication Date: 2016-09-27 PubMed ID: 27729913PubMed Central: PMC5037129DOI: 10.3389/fimmu.2016.00392Google 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 demonstrates that interferon-gamma (IFNγ)-priming intensifies the therapeutic powers of equine mesenchymal stem cells in combating osteoarthritis, as observed in a mouse model. The study suggests promising implications of this regenerative therapy for the treatment of musculoskeletal diseases in horses.

Understanding the Research

The research study was outlined and conducted through a sequence of experimental setups, each uncovering valuable insights. The findings were divided into several different yet interconnected areas:

  • Cells’ Source and Functionality: Mesenchymal stem cells, particularly those derived from adipose tissue (fat), were the primary focus. This category of cells, referred to as ASCs, has shown potential in the regulation and treatment of osteoarthritis in various animal models. Specifically, the study examines equine ASCs (eASCs), given their potential usefulness in treating horses engaged in competitive sports where risk of Osteoarthritis is high.
  • Interferon-Gamma Priming: The methodology of the experiment was to observe the effects of IFNγ-priming on eASCs. By exposing the eASCs to the protein IFNγ before introducing them to the osteoarthritis environment in the mouse model, researchers aimed to analyze any potential enhanced therapeutic benefits.
  • Testing and Analysis: To effectively demonstrate their findings, the researchers isolated eASCs from subcutaneous fat, and their expression of specific markers was tested using cytometry and RT-qPCR. Additionally, naïve or IFNγ-primed eASCs were then cocultured with peripheral blood mononuclear cells or articular cartilage explants.

Findings of the Study

Valuable results arose from the study, painting a promising picture for the therapy’s potential:

  • Chondroprotective Effect: It was observed that the eASCs exhibited a chondroprotective effect. This means that they helped protect the cells of the cartilage from damage and degradation – a basic cause of osteoarthritis.
  • Immunosuppressive Function: Also seen was the immunosuppressive capacity of the eASCs on equine T cell proliferation. This implies the eASCs can suppress the immune response, potentially reducing inflammation and damage caused to joints in OA.
  • IFNγ-Primed eASCs: The IFNγ-priming of eASCs had a heightened effect on both counts, indicating the procedure could be potentially beneficial for bringing about a stronger therapeutic impact.
  • Applicability of Findings: Lastly, findings were considered promising and relevant to manage musculoskeletal diseases in real-world veterinary medicine. This was based on the use of an immunocompetent mouse model to test the therapeutic efficacy of these cells.

Cite This Article

APA
Maumus M, Roussignol G, Toupet K, Penarier G, Bentz I, Teixeira S, Oustric D, Jung M, Lepage O, Steinberg R, Jorgensen C, Noel D. (2016). Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells. Front Immunol, 7, 392. https://doi.org/10.3389/fimmu.2016.00392

Publication

Frontiers in immunology
ISSN: 1664-3224
NlmUniqueID: 101560960
Country: Switzerland
Language: English
Volume: 7
Pages: 392
PII: 392

Researcher Affiliations

Maumus, Marie
  • U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France.
Roussignol, Gautier
  • Sanofi , Montpellier , France.
Toupet, Karine
  • U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France.
Penarier, Geraldine
  • Sanofi , Montpellier , France.
Bentz, Isabelle
  • Sanofi , Montpellier , France.
Teixeira, Sandrine
  • Sanofi , Montpellier , France.
Oustric, Didier
  • Sanofi , Montpellier , France.
Jung, Mireille
  • Sanofi , Montpellier , France.
Lepage, Olivier
  • GREMERES-ICE, University of Lyon , Marcy l'Etoile , France.
Steinberg, Regis
  • Sanofi , Montpellier , France.
Jorgensen, Christian
  • U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France; Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Hôpital Lapeyronie, Montpellier, France.
Noel, Danièle
  • U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France; Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Hôpital Lapeyronie, Montpellier, France.

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