Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes
In recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic c...
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Frontiers Media S.A.
2022-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1041592/full |
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author | Thu Huyen Nguyen Huy Hoang Dao Huy Hoang Dao Chau Minh Duong Chau Minh Duong Xuan-Hung Nguyen Xuan-Hung Nguyen Diem Huong Hoang Xuan-Hai Do Trung Quang Truong Tu Dac Nguyen Liem Thanh Nguyen Liem Thanh Nguyen Uyen Thi Trang Than |
author_facet | Thu Huyen Nguyen Huy Hoang Dao Huy Hoang Dao Chau Minh Duong Chau Minh Duong Xuan-Hung Nguyen Xuan-Hung Nguyen Diem Huong Hoang Xuan-Hai Do Trung Quang Truong Tu Dac Nguyen Liem Thanh Nguyen Liem Thanh Nguyen Uyen Thi Trang Than |
author_sort | Thu Huyen Nguyen |
collection | DOAJ |
description | In recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic chondrocyte physiology. Priming UCMSCs individually with transforming growth factor beta (TGFβ), interferon alpha (IFNα), or tumor necrosis factor alpha (TNFα) significantly reduced the sorting of miR-181b-3p but not miR-320a-3p; two negative regulators of chondrocyte regeneration, into EVs. However, the EV treatment did not show any significant effect on chondrocyte proliferation. Meanwhile, EVs from both non-priming and cytokine-primed UCMSCs induced migration at later time points of measurement. Moreover, TGFβ-primed UCMSCs secreted EVs that could upregulate the expression of chondrogenesis markers (COL2 and ACAN) and downregulate fibrotic markers (COL1 and RUNX2) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders. |
first_indexed | 2024-04-11T08:21:56Z |
format | Article |
id | doaj.art-f56f581cc8ec43b0964a34910b5cf77e |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-11T08:21:56Z |
publishDate | 2022-10-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-f56f581cc8ec43b0964a34910b5cf77e2022-12-22T04:34:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10415921041592Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytesThu Huyen Nguyen0Huy Hoang Dao1Huy Hoang Dao2Chau Minh Duong3Chau Minh Duong4Xuan-Hung Nguyen5Xuan-Hung Nguyen6Diem Huong Hoang7Xuan-Hai Do8Trung Quang Truong9Tu Dac Nguyen10Liem Thanh Nguyen11Liem Thanh Nguyen12Uyen Thi Trang Than13Center of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamCenter of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamFaculty of Biology, VNU University of Science, Vietnam National University, Hanoi, VietnamCenter of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamDepartment of Biology, Clark University, Worcester, MA, United StatesCenter of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamCollege of Health Sciences, VinUniversity, Hanoi, VietnamCenter of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamDepartment of Practical and Experimental Surgery, Vietnam Military Medical University, Hanoi, VietnamHanoi Medical University, Hanoi Medical University Hospital, Hanoi, VietnamCenter of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamCollege of Health Sciences, VinUniversity, Hanoi, VietnamVinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, VietnamCenter of Applied Sciences, Regenerative Medicine and Advance Technologies, Vinmec Healthcare System, Hanoi, VietnamIn recent years, extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) have emerged as a potential cell-free therapy against osteoarthritis (OA). Thus, we investigated the therapeutic effects of EVs released by cytokine-primed umbilical cord-derived MSCs (UCMSCs) on osteoarthritic chondrocyte physiology. Priming UCMSCs individually with transforming growth factor beta (TGFβ), interferon alpha (IFNα), or tumor necrosis factor alpha (TNFα) significantly reduced the sorting of miR-181b-3p but not miR-320a-3p; two negative regulators of chondrocyte regeneration, into EVs. However, the EV treatment did not show any significant effect on chondrocyte proliferation. Meanwhile, EVs from both non-priming and cytokine-primed UCMSCs induced migration at later time points of measurement. Moreover, TGFβ-primed UCMSCs secreted EVs that could upregulate the expression of chondrogenesis markers (COL2 and ACAN) and downregulate fibrotic markers (COL1 and RUNX2) in chondrocytes. Hence, priming UCMSCs with cytokines can deliver selective therapeutic effects of EV treatment in OA and chondrocyte-related disorders.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1041592/fullosteoarthritischondrocytesmesenchymal stem cellsextracellular vesiclescytokinesmicroRNA |
spellingShingle | Thu Huyen Nguyen Huy Hoang Dao Huy Hoang Dao Chau Minh Duong Chau Minh Duong Xuan-Hung Nguyen Xuan-Hung Nguyen Diem Huong Hoang Xuan-Hai Do Trung Quang Truong Tu Dac Nguyen Liem Thanh Nguyen Liem Thanh Nguyen Uyen Thi Trang Than Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes Frontiers in Immunology osteoarthritis chondrocytes mesenchymal stem cells extracellular vesicles cytokines microRNA |
title | Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes |
title_full | Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes |
title_fullStr | Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes |
title_full_unstemmed | Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes |
title_short | Cytokine-primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes |
title_sort | cytokine primed umbilical cord mesenchymal stem cells enhanced therapeutic effects of extracellular vesicles on osteoarthritic chondrocytes |
topic | osteoarthritis chondrocytes mesenchymal stem cells extracellular vesicles cytokines microRNA |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1041592/full |
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