Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium
<b>Background:</b> Radiation cystitis (RC) results from chronic inflammation, fibrosis, and vascular damage. The urinary symptoms it causes have a serious impact on patients’ quality of life. Despite the improvement in irradiation techniques, the incidence of radiation cystitis remains s...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2079-7737/11/7/980 |
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| author | Carole Helissey Nathalie Guitard Hélène Théry Sylvie Goulinet Philippe Mauduit Maria Girleanu Anne-Laure Favier Michel Drouet Charles Parnot Cyrus Chargari Sophie Cavallero Sabine François |
| author_facet | Carole Helissey Nathalie Guitard Hélène Théry Sylvie Goulinet Philippe Mauduit Maria Girleanu Anne-Laure Favier Michel Drouet Charles Parnot Cyrus Chargari Sophie Cavallero Sabine François |
| author_sort | Carole Helissey |
| collection | DOAJ |
| description | <b>Background:</b> Radiation cystitis (RC) results from chronic inflammation, fibrosis, and vascular damage. The urinary symptoms it causes have a serious impact on patients’ quality of life. Despite the improvement in irradiation techniques, the incidence of radiation cystitis remains stable over time, and the therapeutic possibilities remain limited. Mesenchymal stem/stromal cells (MSC) appear to offer<sup>2</sup> a promising therapeutic approach by promoting tissue repair through their paracrine action via extracellular vesicles (MSC-EVs) or conditioned medium from human mesenchymal stromal cells (MSC-CM). We assess the therapeutic potential of MSC-EVs or MSC-CM in an <i>in vitro</i> model of RC. <b>Methods:</b><i>in vitro</i> RC was induced by irradiation of human bladder fibroblasts (HUBF) with the small-animal radiation research platform (SARRP). HUBF were induced towards an RC phenotype after 3 × 3.5 Gy irradiation in the presence of either MSC-EVs or MSC-CM, to assess their effect on fibrosis, angiogenesis, and inflammatory markers. <b>Results:</b> Our data revealed <i>in vitro</i> a higher therapeutic potential of MSC-EVs and MSC-CM in prevention of RC. This was confirmed by down-regulation of α-SMA and CTGF transcription, and the induction of the secretion of anti-fibrotic cytokines, such as IFNγ, IL10 and IL27 and the decrease in the secretion of pro-fibrotic cytokines, IGFBP2, IL1β, IL6, IL18, PDGF, TNFα, and HGF, by irradiated HUBFs, conditioned with MSC-EVs or MSC-CM. The secretome of MSC (MSC-CM) or its subsecretome (MSC-EVs) are proangiogenic, with the ability to induce vessels from HUVEC cells, ensuring the management of bladder vascular lesions induced by irradiation. <b>Conclusion:</b> MSC-EVs and MSC-CM appear to have promising therapeutic potential in the prevention of RC <i>in vitro</i>, by targeting the three main stages of RC: fibrosis, inflammation and vascular damage. |
| first_indexed | 2024-03-09T10:22:46Z |
| format | Article |
| id | doaj.art-f6337130967449fead5c910816569d29 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T10:22:46Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-f6337130967449fead5c910816569d292023-12-01T21:54:18ZengMDPI AGBiology2079-77372022-06-0111798010.3390/biology11070980Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned MediumCarole Helissey0Nathalie Guitard1Hélène Théry2Sylvie Goulinet3Philippe Mauduit4Maria Girleanu5Anne-Laure Favier6Michel Drouet7Charles Parnot8Cyrus Chargari9Sophie Cavallero10Sabine François11Clinical Unit Research, HIA Bégin, 94160 Saint-Mandé, FranceDepartment of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceDepartment of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceTechnical Platform iVEs, UMRS-MD 1197 (INSERM), Paul Brousse Hospital, 94800 Villejuif, FranceTechnical Platform iVEs, UMRS-MD 1197 (INSERM), Paul Brousse Hospital, 94800 Villejuif, FranceImaging Unit, Department of Platforms and Technological Research, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceImaging Unit, Department of Platforms and Technological Research, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceDepartment of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceCureety, 33 rue de l’Amirauté, 22100 Dinan, FranceDepartment of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceDepartment of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, FranceDepartment of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, France<b>Background:</b> Radiation cystitis (RC) results from chronic inflammation, fibrosis, and vascular damage. The urinary symptoms it causes have a serious impact on patients’ quality of life. Despite the improvement in irradiation techniques, the incidence of radiation cystitis remains stable over time, and the therapeutic possibilities remain limited. Mesenchymal stem/stromal cells (MSC) appear to offer<sup>2</sup> a promising therapeutic approach by promoting tissue repair through their paracrine action via extracellular vesicles (MSC-EVs) or conditioned medium from human mesenchymal stromal cells (MSC-CM). We assess the therapeutic potential of MSC-EVs or MSC-CM in an <i>in vitro</i> model of RC. <b>Methods:</b><i>in vitro</i> RC was induced by irradiation of human bladder fibroblasts (HUBF) with the small-animal radiation research platform (SARRP). HUBF were induced towards an RC phenotype after 3 × 3.5 Gy irradiation in the presence of either MSC-EVs or MSC-CM, to assess their effect on fibrosis, angiogenesis, and inflammatory markers. <b>Results:</b> Our data revealed <i>in vitro</i> a higher therapeutic potential of MSC-EVs and MSC-CM in prevention of RC. This was confirmed by down-regulation of α-SMA and CTGF transcription, and the induction of the secretion of anti-fibrotic cytokines, such as IFNγ, IL10 and IL27 and the decrease in the secretion of pro-fibrotic cytokines, IGFBP2, IL1β, IL6, IL18, PDGF, TNFα, and HGF, by irradiated HUBFs, conditioned with MSC-EVs or MSC-CM. The secretome of MSC (MSC-CM) or its subsecretome (MSC-EVs) are proangiogenic, with the ability to induce vessels from HUVEC cells, ensuring the management of bladder vascular lesions induced by irradiation. <b>Conclusion:</b> MSC-EVs and MSC-CM appear to have promising therapeutic potential in the prevention of RC <i>in vitro</i>, by targeting the three main stages of RC: fibrosis, inflammation and vascular damage.https://www.mdpi.com/2079-7737/11/7/980mesenchymal stem/stromal cellsconditioned mediumextracellular vesicleshuman bladder fibroblastsradiation cystitis |
| spellingShingle | Carole Helissey Nathalie Guitard Hélène Théry Sylvie Goulinet Philippe Mauduit Maria Girleanu Anne-Laure Favier Michel Drouet Charles Parnot Cyrus Chargari Sophie Cavallero Sabine François Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium Biology mesenchymal stem/stromal cells conditioned medium extracellular vesicles human bladder fibroblasts radiation cystitis |
| title | Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium |
| title_full | Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium |
| title_fullStr | Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium |
| title_full_unstemmed | Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium |
| title_short | Two New Potential Therapeutic Approaches in Radiation Cystitis Derived from Mesenchymal Stem Cells: Extracellular Vesicles and Conditioned Medium |
| title_sort | two new potential therapeutic approaches in radiation cystitis derived from mesenchymal stem cells extracellular vesicles and conditioned medium |
| topic | mesenchymal stem/stromal cells conditioned medium extracellular vesicles human bladder fibroblasts radiation cystitis |
| url | https://www.mdpi.com/2079-7737/11/7/980 |
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