Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis

Purpose. Adipose-derived mesenchymal stem cells (ADSCs) are increasingly applied in tendon repair. However, the underlying mechanisms of ADSC-derived extracellular vesicles (EVs) in tendon healing are largely unknown. In this study, we investigated the effect of the EVs secreted by ADSCs on the reco...

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Main Authors: Haibo Zhao, Hongyuan Jiang, Haoyun Zhang, Zewen Sun, Qian Lin, Tianrui Wang, Tengbo Yu, Yingze Zhang
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2022/4197473
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author Haibo Zhao
Hongyuan Jiang
Haoyun Zhang
Zewen Sun
Qian Lin
Tianrui Wang
Tengbo Yu
Yingze Zhang
author_facet Haibo Zhao
Hongyuan Jiang
Haoyun Zhang
Zewen Sun
Qian Lin
Tianrui Wang
Tengbo Yu
Yingze Zhang
author_sort Haibo Zhao
collection DOAJ
description Purpose. Adipose-derived mesenchymal stem cells (ADSCs) are increasingly applied in tendon repair. However, the underlying mechanisms of ADSC-derived extracellular vesicles (EVs) in tendon healing are largely unknown. In this study, we investigated the effect of the EVs secreted by ADSCs on the recovery of tendon injuries and its potential mechanism. Materials and Methods. We injected ADSCs into the injured tendon, followed by the evaluation of the tissue morphology, tenocyte proliferation, and oxidative stress. Then, the injured tenocytes were treated with EVs secreted by ADSCs, and oxidative stress and proliferation of tenocytes in vitro were detected. After the overexpression and knockdown of miR-19a and its target protein IGFBP3, the oxidative stress and proliferation of tenocytes in vitro were assessed. Finally, the injured tendon was treated with EVs, and the tissue morphology and proliferation of the injured tendon in vivo were examined. Results. ADSC-derived EVs were found to inhibit oxidative stress and promote proliferation of tenocytes isolated from an injury model of rats. EVs were shown to carry miR-19a which regulated the expression of IGFBP3 through binding to 3′UTR of IGFBP3 mRNA. In addition, IGFBP3 promotes oxidative stress and inhibits proliferation of tenocytes. Finally, we found that ADSC-derived EVs promoted tendon wound healing in vivo. Conclusions. Our data suggest that treatment with ADSC-derived EVs ameliorates tendon injury by inhibiting oxidative stress and promoting proliferation in tenocytes. miR-19a carried by ADSC-derived EVs regulates IGFBP3 expression through binding to its 3′UTR.
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spelling doaj-art-065aa7bfcd8946a6aa2f0cd8e5f2a7f82025-08-20T02:03:42ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/4197473Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 AxisHaibo Zhao0Hongyuan Jiang1Haoyun Zhang2Zewen Sun3Qian Lin4Tianrui Wang5Tengbo Yu6Yingze Zhang7Department of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsTrauma and Emergency CenterPurpose. Adipose-derived mesenchymal stem cells (ADSCs) are increasingly applied in tendon repair. However, the underlying mechanisms of ADSC-derived extracellular vesicles (EVs) in tendon healing are largely unknown. In this study, we investigated the effect of the EVs secreted by ADSCs on the recovery of tendon injuries and its potential mechanism. Materials and Methods. We injected ADSCs into the injured tendon, followed by the evaluation of the tissue morphology, tenocyte proliferation, and oxidative stress. Then, the injured tenocytes were treated with EVs secreted by ADSCs, and oxidative stress and proliferation of tenocytes in vitro were detected. After the overexpression and knockdown of miR-19a and its target protein IGFBP3, the oxidative stress and proliferation of tenocytes in vitro were assessed. Finally, the injured tendon was treated with EVs, and the tissue morphology and proliferation of the injured tendon in vivo were examined. Results. ADSC-derived EVs were found to inhibit oxidative stress and promote proliferation of tenocytes isolated from an injury model of rats. EVs were shown to carry miR-19a which regulated the expression of IGFBP3 through binding to 3′UTR of IGFBP3 mRNA. In addition, IGFBP3 promotes oxidative stress and inhibits proliferation of tenocytes. Finally, we found that ADSC-derived EVs promoted tendon wound healing in vivo. Conclusions. Our data suggest that treatment with ADSC-derived EVs ameliorates tendon injury by inhibiting oxidative stress and promoting proliferation in tenocytes. miR-19a carried by ADSC-derived EVs regulates IGFBP3 expression through binding to its 3′UTR.http://dx.doi.org/10.1155/2022/4197473
spellingShingle Haibo Zhao
Hongyuan Jiang
Haoyun Zhang
Zewen Sun
Qian Lin
Tianrui Wang
Tengbo Yu
Yingze Zhang
Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis
Stem Cells International
title Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis
title_full Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis
title_fullStr Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis
title_full_unstemmed Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis
title_short Adipose-Derived Mesenchymal Stem Cell-Derived Extracellular Vesicles Rescue Tendon Injury in Rat via the miR-19 a/IGFBP3 Axis
title_sort adipose derived mesenchymal stem cell derived extracellular vesicles rescue tendon injury in rat via the mir 19 a igfbp3 axis
url http://dx.doi.org/10.1155/2022/4197473
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