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

View Article: PubMed Central - PubMed

ABSTRACT

Objective: 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 in vitro. 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.

Conclusion: 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.

No MeSH data available.


Xenogeneic eASCs improve OA scores in the collagenase-induced OA mouse model. OA was induced by intra-articular injection of collagenase in mouse knee joints and the severity of OA was evaluated at day 42. (A) Representative photographs of knee joints from control (collagenase alone) (upper), mMSCs-treated (middle), and eASCs-treated (lower) mice. (B) Histological OA score of tibia plateaus and femur condyles in the mouse knee joints and mean at euthanasia. Results are expressed as the mean ± SEM, n = 10. Data were analyzed using the Kruskal–Wallis test followed by Dunn’s test for multiple comparisons. *p < 0.05.
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Figure 3: Xenogeneic eASCs improve OA scores in the collagenase-induced OA mouse model. OA was induced by intra-articular injection of collagenase in mouse knee joints and the severity of OA was evaluated at day 42. (A) Representative photographs of knee joints from control (collagenase alone) (upper), mMSCs-treated (middle), and eASCs-treated (lower) mice. (B) Histological OA score of tibia plateaus and femur condyles in the mouse knee joints and mean at euthanasia. Results are expressed as the mean ± SEM, n = 10. Data were analyzed using the Kruskal–Wallis test followed by Dunn’s test for multiple comparisons. *p < 0.05.

Mentions: We, then, investigated whether eASCs could exert a therapeutic effect in vivo using a xenogeneic relevant model of OA. We used the CIOA mouse model which is characterized by moderate inflammation of the synovial membrane, osteophyte formation, and cartilage degradation (18). First, we evaluated the effect of intra-articular injection of eASCs (2 × 105 cells) on knee joint OA score by comparison with mMSCs (2 × 105 cells). Histological analysis of knee joint sections revealed protection against cartilage degradation in animals treated either with mMSCs or eASCs as compared with the CIOA control group (Figure 3A). Cartilage protective effect of mMSCs and eASCs was confirmed by scoring both femoral condyles and tibial plateaux in the lateral and medial compartments (Figure 3B). Significantly, lower mean OA scores were obtained after eASCs or mMSCs treatment, and OA score of the eASC group was highly significant compared to control group. These results confirmed that the CIOA mouse model was effective for evaluation of the effect of xenogeneic eASC injection on OA symptoms.


Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFN γ -Primed Equine Mesenchymal Stem Cells
Xenogeneic eASCs improve OA scores in the collagenase-induced OA mouse model. OA was induced by intra-articular injection of collagenase in mouse knee joints and the severity of OA was evaluated at day 42. (A) Representative photographs of knee joints from control (collagenase alone) (upper), mMSCs-treated (middle), and eASCs-treated (lower) mice. (B) Histological OA score of tibia plateaus and femur condyles in the mouse knee joints and mean at euthanasia. Results are expressed as the mean ± SEM, n = 10. Data were analyzed using the Kruskal–Wallis test followed by Dunn’s test for multiple comparisons. *p < 0.05.
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Figure 3: Xenogeneic eASCs improve OA scores in the collagenase-induced OA mouse model. OA was induced by intra-articular injection of collagenase in mouse knee joints and the severity of OA was evaluated at day 42. (A) Representative photographs of knee joints from control (collagenase alone) (upper), mMSCs-treated (middle), and eASCs-treated (lower) mice. (B) Histological OA score of tibia plateaus and femur condyles in the mouse knee joints and mean at euthanasia. Results are expressed as the mean ± SEM, n = 10. Data were analyzed using the Kruskal–Wallis test followed by Dunn’s test for multiple comparisons. *p < 0.05.
Mentions: We, then, investigated whether eASCs could exert a therapeutic effect in vivo using a xenogeneic relevant model of OA. We used the CIOA mouse model which is characterized by moderate inflammation of the synovial membrane, osteophyte formation, and cartilage degradation (18). First, we evaluated the effect of intra-articular injection of eASCs (2 × 105 cells) on knee joint OA score by comparison with mMSCs (2 × 105 cells). Histological analysis of knee joint sections revealed protection against cartilage degradation in animals treated either with mMSCs or eASCs as compared with the CIOA control group (Figure 3A). Cartilage protective effect of mMSCs and eASCs was confirmed by scoring both femoral condyles and tibial plateaux in the lateral and medial compartments (Figure 3B). Significantly, lower mean OA scores were obtained after eASCs or mMSCs treatment, and OA score of the eASC group was highly significant compared to control group. These results confirmed that the CIOA mouse model was effective for evaluation of the effect of xenogeneic eASC injection on OA symptoms.

View Article: PubMed Central - PubMed

ABSTRACT

Objective: 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 (IFN&gamma;)-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, na&iuml;ve or IFN&gamma;-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 in vitro. Both cartilage degradation and T cell activation were reduced by na&iuml;ve and IFN&gamma;-primed eASCs, but IFN&gamma;-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFN&gamma;-primed eASCs were more potent than na&iuml;ve cells. This effect was related to the modulation of eASC secretome by IFN&gamma;-priming.

Conclusion: IFN&gamma;-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 IFN&gamma;-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine.

No MeSH data available.