Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma
Abstract Background Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effe...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-017-0600-8 |
| _version_ | 1819178865883348992 |
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| author | Ligia Lins de Castro Debora Gonçalves Xisto Jamil Zola Kitoko Fernanda Ferreira Cruz Priscilla Christina Olsen Patricia Albuquerque Garcia Redondo Tatiana Paula Teixeira Ferreira Daniel Jay Weiss Marco Aurélio Martins Marcelo Marcos Morales Patricia Rieken Macedo Rocco |
| author_facet | Ligia Lins de Castro Debora Gonçalves Xisto Jamil Zola Kitoko Fernanda Ferreira Cruz Priscilla Christina Olsen Patricia Albuquerque Garcia Redondo Tatiana Paula Teixeira Ferreira Daniel Jay Weiss Marco Aurélio Martins Marcelo Marcos Morales Patricia Rieken Macedo Rocco |
| author_sort | Ligia Lins de Castro |
| collection | DOAJ |
| description | Abstract Background Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. Methods C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 105 human AD-MSCs, or EVs (released by 105 AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. Results In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3+CD4+ T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3+CD4+ T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3+CD4+ T cells in the mediastinal lymph nodes. Conclusions In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different mechanisms of action of AD-MSCs versus their EVs. |
| first_indexed | 2024-12-22T21:49:21Z |
| format | Article |
| id | doaj.art-b320d3c1737f4cab83be271d27c4c705 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-22T21:49:21Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-b320d3c1737f4cab83be271d27c4c7052022-12-21T18:11:25ZengBMCStem Cell Research & Therapy1757-65122017-06-018111210.1186/s13287-017-0600-8Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthmaLigia Lins de Castro0Debora Gonçalves Xisto1Jamil Zola Kitoko2Fernanda Ferreira Cruz3Priscilla Christina Olsen4Patricia Albuquerque Garcia Redondo5Tatiana Paula Teixeira Ferreira6Daniel Jay Weiss7Marco Aurélio Martins8Marcelo Marcos Morales9Patricia Rieken Macedo Rocco10Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de JaneiroLaboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de JaneiroLaboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de JaneiroLaboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de JaneiroLaboratory of Clinical Bacteriology and Immunology, Health Sciences Center, Federal University of Rio de JaneiroProgram of Morphological Sciences, Biomedical Sciences Institute, Federal University of Rio de JaneiroLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz FoundationDepartment of Medicine, University of Vermont, College of MedicineLaboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz FoundationLaboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de JaneiroLaboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de JaneiroAbstract Background Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. Methods C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 105 human AD-MSCs, or EVs (released by 105 AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. Results In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3+CD4+ T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3+CD4+ T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3+CD4+ T cells in the mediastinal lymph nodes. Conclusions In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different mechanisms of action of AD-MSCs versus their EVs.http://link.springer.com/article/10.1186/s13287-017-0600-8AsthmaRemodelingMesenchymal stromal cellsExtracellular vesiclesInflammation |
| spellingShingle | Ligia Lins de Castro Debora Gonçalves Xisto Jamil Zola Kitoko Fernanda Ferreira Cruz Priscilla Christina Olsen Patricia Albuquerque Garcia Redondo Tatiana Paula Teixeira Ferreira Daniel Jay Weiss Marco Aurélio Martins Marcelo Marcos Morales Patricia Rieken Macedo Rocco Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma Stem Cell Research & Therapy Asthma Remodeling Mesenchymal stromal cells Extracellular vesicles Inflammation |
| title | Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma |
| title_full | Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma |
| title_fullStr | Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma |
| title_full_unstemmed | Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma |
| title_short | Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma |
| title_sort | human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma |
| topic | Asthma Remodeling Mesenchymal stromal cells Extracellular vesicles Inflammation |
| url | http://link.springer.com/article/10.1186/s13287-017-0600-8 |
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