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Article

Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis

1
IRMB, University of Montpellier, INSERM, 34295 Montpellier, France
2
Department of Internal Medicine, Multi-Organic Diseases, CHU, 34295 Montpellier, France
3
Clinical Immunology and Osteoarticular Disease Therapeutic Unit, Department of Rheumatology, CHU, 34295 Montpellier, France
*
Author to whom correspondence should be addressed.
Academic Editor: Nicoletta Del Papa
Cells 2021, 10(10), 2727; https://doi.org/10.3390/cells10102727
Received: 20 September 2021 / Revised: 4 October 2021 / Accepted: 7 October 2021 / Published: 13 October 2021
(This article belongs to the Special Issue Mesenchymal Stem Cell-Derived Extracellular Vesicles)
Background: Systemic sclerosis (SSc) is a severe autoimmune disease for which mesenchymal stromal cells (MSCs)-based therapy was reported to reduce SSc-related symptoms in pre-clinical studies. Recently, extracellular vesicles released by MSCs (MSC-EVs) were shown to mediate most of their therapeutic effect. Here, we aimed at improving their efficacy by increasing the MSC-EV dose or by IFNγ-priming of MSCs. Methods: small size (ssEVs) and large size EVs (lsEVs) were recovered from murine MSCs that were pre-activated using 1 or 20 ng/mL of IFNγ. In the HOCl-induced model of SSc, mice were treated with EVs at day 21 and sacrificed at day 42. Lung and skin samples were collected for histological and molecular analyses. Results: increasing the dose of MSC-EVs did not add benefit to the dose previously reported to be efficient in SSc. By contrast, IFNγ pre-activation improved MSC-EVs-based treatment, essentially in the lungs. Low doses of IFNγ decreased the expression of fibrotic markers, while high doses improved remodeling and anti-inflammatory markers. IFNγ pre-activation upregulated iNos, IL1ra and Il6 in MSCs and ssEVs and the PGE2 protein in lsEVs. Conclusion: IFNγ-pre-activation improved the therapeutic effect of MSC-EVs preferentially in the lungs of SSc mice by modulating anti-inflammatory and anti-fibrotic markers. View Full-Text
Keywords: mesenchymal stromal cell; scleroderma; extracellular vesicles; exosomes; microvesicles; therapy mesenchymal stromal cell; scleroderma; extracellular vesicles; exosomes; microvesicles; therapy
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MDPI and ACS Style

Rozier, P.; Maumus, M.; Maria, A.T.J.; Toupet, K.; Jorgensen, C.; Guilpain, P.; Noël, D. Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis. Cells 2021, 10, 2727. https://doi.org/10.3390/cells10102727

AMA Style

Rozier P, Maumus M, Maria ATJ, Toupet K, Jorgensen C, Guilpain P, Noël D. Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis. Cells. 2021; 10(10):2727. https://doi.org/10.3390/cells10102727

Chicago/Turabian Style

Rozier, Pauline, Marie Maumus, Alexandre T.J. Maria, Karine Toupet, Christian Jorgensen, Philippe Guilpain, and Danièle Noël. 2021. "Lung Fibrosis Is Improved by Extracellular Vesicles from IFNγ-Primed Mesenchymal Stromal Cells in Murine Systemic Sclerosis" Cells 10, no. 10: 2727. https://doi.org/10.3390/cells10102727

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