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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Main Authors: Thu Huyen Nguyen, Huy Hoang Dao, Chau Minh Duong, Xuan-Hung Nguyen, Diem Huong Hoang, Xuan-Hai Do, Trung Quang Truong, Tu Dac Nguyen, Liem Thanh Nguyen, Uyen Thi Trang Than
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Immunology
Subjects:
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.
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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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