HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures

Abstract The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicle...

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Main Authors: Zhian Chen, Tianhua Zhou, Huan Luo, Zhen Wang, Qiang Wang, Rongmao Shi, Zian Li, Rongqing Pang, Hongbo Tan
Format: Article
Language:English
Published: BMC 2024-04-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-024-02451-2
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author Zhian Chen
Tianhua Zhou
Huan Luo
Zhen Wang
Qiang Wang
Rongmao Shi
Zian Li
Rongqing Pang
Hongbo Tan
author_facet Zhian Chen
Tianhua Zhou
Huan Luo
Zhen Wang
Qiang Wang
Rongmao Shi
Zian Li
Rongqing Pang
Hongbo Tan
author_sort Zhian Chen
collection DOAJ
description Abstract The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery. Graphical abstract
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spelling doaj.art-05aaf9f00a754d34b6ec5c36b83fae082024-04-14T11:28:08ZengBMCJournal of Nanobiotechnology1477-31552024-04-0122112010.1186/s12951-024-02451-2HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfracturesZhian Chen0Tianhua Zhou1Huan Luo2Zhen Wang3Qiang Wang4Rongmao Shi5Zian Li6Rongqing Pang7Hongbo Tan8Graduate School, Kunming Medical UniversityDepartment of Orthopaedics, People’s Liberation Army Joint Logistic Support Force 920th HospitalGraduate School, Kunming Medical UniversityGraduate School, Kunming Medical UniversityBasic Medical Laboratory, People’s Liberation Army Joint Logistic Support Force 920th HospitalDepartment of Orthopaedics, People’s Liberation Army Joint Logistic Support Force 920th HospitalBasic Medical Laboratory, People’s Liberation Army Joint Logistic Support Force 920th HospitalBasic Medical Laboratory, People’s Liberation Army Joint Logistic Support Force 920th HospitalDepartment of Orthopaedics, People’s Liberation Army Joint Logistic Support Force 920th HospitalAbstract The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery. Graphical abstracthttps://doi.org/10.1186/s12951-024-02451-2ChondrocytesRegenerationMicrofracturesHuman Wharton’s jelly MSCsExtracellular vesicles
spellingShingle Zhian Chen
Tianhua Zhou
Huan Luo
Zhen Wang
Qiang Wang
Rongmao Shi
Zian Li
Rongqing Pang
Hongbo Tan
HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
Journal of Nanobiotechnology
Chondrocytes
Regeneration
Microfractures
Human Wharton’s jelly MSCs
Extracellular vesicles
title HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
title_full HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
title_fullStr HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
title_full_unstemmed HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
title_short HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures
title_sort hwjmsc evs promote cartilage regeneration and repair via the itgb1 tgf β smad2 3 axis mediated by microfractures
topic Chondrocytes
Regeneration
Microfractures
Human Wharton’s jelly MSCs
Extracellular vesicles
url https://doi.org/10.1186/s12951-024-02451-2
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