Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis
Systemic sclerosis (SSc) is a complex disorder resulting from dysregulated interactions between the three main pathophysiological axes: fibrosis, immune dysfunction, and vasculopathy, with no specific treatment available to date. Adipose tissue-derived mesenchymal stromal cells (ASCs) and their extr...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6837 |
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| author | Pauline Rozier Marie Maumus Claire Bony Alexandre Thibault Jacques Maria Florence Sabatier Christian Jorgensen Philippe Guilpain Danièle Noël |
| author_facet | Pauline Rozier Marie Maumus Claire Bony Alexandre Thibault Jacques Maria Florence Sabatier Christian Jorgensen Philippe Guilpain Danièle Noël |
| author_sort | Pauline Rozier |
| collection | DOAJ |
| description | Systemic sclerosis (SSc) is a complex disorder resulting from dysregulated interactions between the three main pathophysiological axes: fibrosis, immune dysfunction, and vasculopathy, with no specific treatment available to date. Adipose tissue-derived mesenchymal stromal cells (ASCs) and their extracellular vesicles (EVs) have proved efficacy in pre-clinical murine models of SSc. However, their precise action mechanism is still not fully understood. Because of the lack of availability of fibroblasts isolated from SSc patients (SSc-Fb), our aim was to determine whether a TGFβ1-induced model of human myofibroblasts (Tβ-Fb) could reproduce the characteristics of SSc-Fb and be used to evaluate the anti-fibrotic function of ASCs and their EVs. We found out that Tβ-Fb displayed the main morphological and molecular features of SSc-Fb, including the enlarged hypertrophic morphology and expression of several markers associated with the myofibroblastic phenotype. Using this model, we showed that ASCs were able to regulate the expression of most myofibroblastic markers on Tβ-Fb and SSc-Fb, but only when pre-stimulated with TGFβ1. Of interest, ASC-derived EVs were more effective than parental cells for improving the myofibroblastic phenotype. In conclusion, we provided evidence that Tβ-Fb are a relevant model to mimic the main characteristics of SSc fibroblasts and investigate the mechanism of action of ASCs. We further reported that ASC-EVs are more effective than parental cells suggesting that the TGFβ1-induced pro-fibrotic environment may alter the function of ASCs. |
| first_indexed | 2024-03-10T10:03:19Z |
| format | Article |
| id | doaj.art-263dd0f2d19c4fc5a934264a5c1184f5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:03:19Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-263dd0f2d19c4fc5a934264a5c1184f52023-11-22T01:45:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213683710.3390/ijms22136837Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic SclerosisPauline Rozier0Marie Maumus1Claire Bony2Alexandre Thibault Jacques Maria3Florence Sabatier4Christian Jorgensen5Philippe Guilpain6Danièle Noël7INSERM U1183, Hôpital Saint-Eloi, IRMB, University of Montpellier, 80 Avenue Augustin Fliche, CEDEX 5, 34295 Montpellier, FranceINSERM U1183, Hôpital Saint-Eloi, IRMB, University of Montpellier, 80 Avenue Augustin Fliche, CEDEX 5, 34295 Montpellier, FranceINSERM U1183, Hôpital Saint-Eloi, IRMB, University of Montpellier, 80 Avenue Augustin Fliche, CEDEX 5, 34295 Montpellier, FranceDepartment of Internal Medicine, Multi-Organic Diseases, CHU, 34295 Montpellier, FranceINSERM, INRA, C2VN, Aix Marseille University, 13005 Marseille, FranceINSERM U1183, Hôpital Saint-Eloi, IRMB, University of Montpellier, 80 Avenue Augustin Fliche, CEDEX 5, 34295 Montpellier, FranceINSERM U1183, Hôpital Saint-Eloi, IRMB, University of Montpellier, 80 Avenue Augustin Fliche, CEDEX 5, 34295 Montpellier, FranceINSERM U1183, Hôpital Saint-Eloi, IRMB, University of Montpellier, 80 Avenue Augustin Fliche, CEDEX 5, 34295 Montpellier, FranceSystemic sclerosis (SSc) is a complex disorder resulting from dysregulated interactions between the three main pathophysiological axes: fibrosis, immune dysfunction, and vasculopathy, with no specific treatment available to date. Adipose tissue-derived mesenchymal stromal cells (ASCs) and their extracellular vesicles (EVs) have proved efficacy in pre-clinical murine models of SSc. However, their precise action mechanism is still not fully understood. Because of the lack of availability of fibroblasts isolated from SSc patients (SSc-Fb), our aim was to determine whether a TGFβ1-induced model of human myofibroblasts (Tβ-Fb) could reproduce the characteristics of SSc-Fb and be used to evaluate the anti-fibrotic function of ASCs and their EVs. We found out that Tβ-Fb displayed the main morphological and molecular features of SSc-Fb, including the enlarged hypertrophic morphology and expression of several markers associated with the myofibroblastic phenotype. Using this model, we showed that ASCs were able to regulate the expression of most myofibroblastic markers on Tβ-Fb and SSc-Fb, but only when pre-stimulated with TGFβ1. Of interest, ASC-derived EVs were more effective than parental cells for improving the myofibroblastic phenotype. In conclusion, we provided evidence that Tβ-Fb are a relevant model to mimic the main characteristics of SSc fibroblasts and investigate the mechanism of action of ASCs. We further reported that ASC-EVs are more effective than parental cells suggesting that the TGFβ1-induced pro-fibrotic environment may alter the function of ASCs.https://www.mdpi.com/1422-0067/22/13/6837systemic sclerosismesenchymal stem cellsTGFβ1anti-fibroticextracellular vesicles |
| spellingShingle | Pauline Rozier Marie Maumus Claire Bony Alexandre Thibault Jacques Maria Florence Sabatier Christian Jorgensen Philippe Guilpain Danièle Noël Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis International Journal of Molecular Sciences systemic sclerosis mesenchymal stem cells TGFβ1 anti-fibrotic extracellular vesicles |
| title | Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis |
| title_full | Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis |
| title_fullStr | Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis |
| title_full_unstemmed | Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis |
| title_short | Extracellular Vesicles Are More Potent Than Adipose Mesenchymal Stromal Cells to Exert an Anti-Fibrotic Effect in an In Vitro Model of Systemic Sclerosis |
| title_sort | extracellular vesicles are more potent than adipose mesenchymal stromal cells to exert an anti fibrotic effect in an in vitro model of systemic sclerosis |
| topic | systemic sclerosis mesenchymal stem cells TGFβ1 anti-fibrotic extracellular vesicles |
| url | https://www.mdpi.com/1422-0067/22/13/6837 |
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