Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MS...
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| Format: | Article |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.627605/full |
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| author | Anna Maria Tolomeo Anna Maria Tolomeo Anna Maria Tolomeo Ignazio Castagliuolo Martina Piccoli Michele Grassi Fabio Magarotto Fabio Magarotto Giada De Lazzari Giada De Lazzari Giada De Lazzari Ricardo Malvicini Ricardo Malvicini Ricardo Malvicini Federico Caicci Chiara Franzin Melania Scarpa Veronica Macchi Raffaele De Caro Raffaele De Caro Imerio Angriman Antonella Viola Andrea Porzionato Andrea Porzionato Michela Pozzobon Michela Pozzobon Maurizio Muraca Maurizio Muraca Maurizio Muraca |
| author_facet | Anna Maria Tolomeo Anna Maria Tolomeo Anna Maria Tolomeo Ignazio Castagliuolo Martina Piccoli Michele Grassi Fabio Magarotto Fabio Magarotto Giada De Lazzari Giada De Lazzari Giada De Lazzari Ricardo Malvicini Ricardo Malvicini Ricardo Malvicini Federico Caicci Chiara Franzin Melania Scarpa Veronica Macchi Raffaele De Caro Raffaele De Caro Imerio Angriman Antonella Viola Andrea Porzionato Andrea Porzionato Michela Pozzobon Michela Pozzobon Maurizio Muraca Maurizio Muraca Maurizio Muraca |
| author_sort | Anna Maria Tolomeo |
| collection | DOAJ |
| description | Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin. |
| first_indexed | 2024-12-14T12:40:01Z |
| format | Article |
| id | doaj.art-7c6bb7f06a8d4a1aa637712b09ffa940 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T12:40:01Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7c6bb7f06a8d4a1aa637712b09ffa9402022-12-21T23:00:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.627605627605Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced ColitisAnna Maria Tolomeo0Anna Maria Tolomeo1Anna Maria Tolomeo2Ignazio Castagliuolo3Martina Piccoli4Michele Grassi5Fabio Magarotto6Fabio Magarotto7Giada De Lazzari8Giada De Lazzari9Giada De Lazzari10Ricardo Malvicini11Ricardo Malvicini12Ricardo Malvicini13Federico Caicci14Chiara Franzin15Melania Scarpa16Veronica Macchi17Raffaele De Caro18Raffaele De Caro19Imerio Angriman20Antonella Viola21Andrea Porzionato22Andrea Porzionato23Michela Pozzobon24Michela Pozzobon25Maurizio Muraca26Maurizio Muraca27Maurizio Muraca28Department of Women’s and Children’s Health, University of Padova, Padua, ItalyLaboratory of Extracellular Vesicles as Therapeutic Tools, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Padua, ItalyDepartment of Molecular Medicine, University of Padova, Padua, ItalyLaboratory of Tissue Engineering, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyDepartment of Women’s and Children’s Health, University of Padova, Padua, ItalyDepartment of Women’s and Children’s Health, University of Padova, Padua, ItalyLaboratory of Stem Cells and Regenerative Medicine, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyDepartment of Women’s and Children’s Health, University of Padova, Padua, ItalyLaboratory of Extracellular Vesicles as Therapeutic Tools, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Padua, ItalyLaboratory of Extracellular Vesicles as Therapeutic Tools, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Padua, ItalyInstituto de medicina traslacional, trasplante y bioingenieria (IMeTTyB-CONICET), Buenos Aires, ArgentinaDepartment of Biology, University of Padova, Padua, ItalyLaboratory of Tissue Engineering, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyLaboratory of Advanced Translational Research, Veneto Institute of Oncology IOV–IRCCS, Padua, Italy0Department of Neurosciences, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Padua, Italy0Department of Neurosciences, University of Padova, Padua, Italy1Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy2Department of Biomedical Sciences, University of Padova, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Padua, Italy0Department of Neurosciences, University of Padova, Padua, ItalyDepartment of Women’s and Children’s Health, University of Padova, Padua, ItalyLaboratory of Stem Cells and Regenerative Medicine, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyDepartment of Women’s and Children’s Health, University of Padova, Padua, ItalyLaboratory of Extracellular Vesicles as Therapeutic Tools, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, ItalyL.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Padua, ItalySeveral reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.https://www.frontiersin.org/articles/10.3389/fimmu.2021.627605/fullinflammatory bowel diseasemesenchymal stromal cellsextracellular vesiclesmacrophage polarizationsodium dextran sulfateimmunomodulation |
| spellingShingle | Anna Maria Tolomeo Anna Maria Tolomeo Anna Maria Tolomeo Ignazio Castagliuolo Martina Piccoli Michele Grassi Fabio Magarotto Fabio Magarotto Giada De Lazzari Giada De Lazzari Giada De Lazzari Ricardo Malvicini Ricardo Malvicini Ricardo Malvicini Federico Caicci Chiara Franzin Melania Scarpa Veronica Macchi Raffaele De Caro Raffaele De Caro Imerio Angriman Antonella Viola Andrea Porzionato Andrea Porzionato Michela Pozzobon Michela Pozzobon Maurizio Muraca Maurizio Muraca Maurizio Muraca Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis Frontiers in Immunology inflammatory bowel disease mesenchymal stromal cells extracellular vesicles macrophage polarization sodium dextran sulfate immunomodulation |
| title | Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis |
| title_full | Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis |
| title_fullStr | Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis |
| title_full_unstemmed | Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis |
| title_short | Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis |
| title_sort | extracellular vesicles secreted by mesenchymal stromal cells exert opposite effects to their cells of origin in murine sodium dextran sulfate induced colitis |
| topic | inflammatory bowel disease mesenchymal stromal cells extracellular vesicles macrophage polarization sodium dextran sulfate immunomodulation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.627605/full |
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