Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties
Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs sec...
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MDPI AG
2021-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/2/209 |
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| author | Hansol Joo Mi-Kyung Oh Ji Yeon Kang Hyun Sung Park Dong-Hoon Chae Jieun Kim Jong-Hee Lee Hee Min Yoo Uimook Choi Do-Kyun Kim Hakmo Lee Sungjoo Kim Kyung-Rok Yu |
| author_facet | Hansol Joo Mi-Kyung Oh Ji Yeon Kang Hyun Sung Park Dong-Hoon Chae Jieun Kim Jong-Hee Lee Hee Min Yoo Uimook Choi Do-Kyun Kim Hakmo Lee Sungjoo Kim Kyung-Rok Yu |
| author_sort | Hansol Joo |
| collection | DOAJ |
| description | Therapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)-primed human Wharton’s jelly-derived MSCs (WJ-MSCs). EVs from TSG-primed WJ-MSCs (TSG-EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor-β1 (TGFβ), cyclooxygenase-2 (COX2), and especially indoleamine 2,3-dioxygenase (IDO), compared to control EVs. TSG-EV showed a significantly enhanced immunosuppressive effect on human peripheral blood-derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2-type macrophage were enriched compared to a control EV-treated group. Furthermore, TSG-EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2-type macrophages in colitic colons of a TSG-EV-treated mouse suggests an anti-inflammatory effect of TSG-EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ-MSCs, and TSG-EV may provide a new therapeutic approach for treatment of colitis. |
| first_indexed | 2024-03-09T00:45:40Z |
| format | Article |
| id | doaj.art-71f8c2c5c8464eb596ffdc5d4e4d28f1 |
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| language | English |
| last_indexed | 2024-03-09T00:45:40Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-71f8c2c5c8464eb596ffdc5d4e4d28f12023-12-11T17:31:57ZengMDPI AGBiomedicines2227-90592021-02-019220910.3390/biomedicines9020209Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory PropertiesHansol Joo0Mi-Kyung Oh1Ji Yeon Kang2Hyun Sung Park3Dong-Hoon Chae4Jieun Kim5Jong-Hee Lee6Hee Min Yoo7Uimook Choi8Do-Kyun Kim9Hakmo Lee10Sungjoo Kim11Kyung-Rok Yu12Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaNational Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, KoreaBiometrology Group, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, KoreaLaboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD 20892, USACenter for Biomolecular and Cellular Structure, Institute for Basic Science (IBS), Daejeon 34126, KoreaDesign One Health Inc., Guri 11906, KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, KoreaTherapeutic applications of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have attracted considerable attention because of their immunomodulatory properties against immune-mediated, inflammatory diseases. Here, we demonstrated enhanced immunomodulatory properties of EVs secreted from endoplasmic reticulum (ER) stress inducer thapsigargin (TSG)-primed human Wharton’s jelly-derived MSCs (WJ-MSCs). EVs from TSG-primed WJ-MSCs (TSG-EV) showed increased yield and expression of immunomodulatory factors, such as transforming growth factor-β1 (TGFβ), cyclooxygenase-2 (COX2), and especially indoleamine 2,3-dioxygenase (IDO), compared to control EVs. TSG-EV showed a significantly enhanced immunosuppressive effect on human peripheral blood-derived T cell proliferation and Th1 and Th17 differentiation, whereas Treg and M2-type macrophage were enriched compared to a control EV-treated group. Furthermore, TSG-EV substantially mitigated mouse experimental colitis by reducing the inflammatory response and maintaining intestinal barrier integrity. A significant increase of Tregs and M2-type macrophages in colitic colons of a TSG-EV-treated mouse suggests an anti-inflammatory effect of TSG-EV in colitis model, possibly mediated by Treg and macrophage polarization. These data indicate that TSG treatment promoted immunomodulatory properties of EVs from WJ-MSCs, and TSG-EV may provide a new therapeutic approach for treatment of colitis.https://www.mdpi.com/2227-9059/9/2/209EVsmesenchymal stem cellsthapsigarginimmunomodulatory propertyindoleamine 2,3-dioxygenase (IDO)colitis model |
| spellingShingle | Hansol Joo Mi-Kyung Oh Ji Yeon Kang Hyun Sung Park Dong-Hoon Chae Jieun Kim Jong-Hee Lee Hee Min Yoo Uimook Choi Do-Kyun Kim Hakmo Lee Sungjoo Kim Kyung-Rok Yu Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties Biomedicines EVs mesenchymal stem cells thapsigargin immunomodulatory property indoleamine 2,3-dioxygenase (IDO) colitis model |
| title | Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties |
| title_full | Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties |
| title_fullStr | Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties |
| title_full_unstemmed | Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties |
| title_short | Extracellular Vesicles from Thapsigargin-Treated Mesenchymal Stem Cells Ameliorated Experimental Colitis via Enhanced Immunomodulatory Properties |
| title_sort | extracellular vesicles from thapsigargin treated mesenchymal stem cells ameliorated experimental colitis via enhanced immunomodulatory properties |
| topic | EVs mesenchymal stem cells thapsigargin immunomodulatory property indoleamine 2,3-dioxygenase (IDO) colitis model |
| url | https://www.mdpi.com/2227-9059/9/2/209 |
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