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HWJMSC-EVs 通过微骨折介导的 ITGB1/TGF-β/Smad2/3 轴促进软骨再生和修复。

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

机构信息

Graduate School, Kunming Medical University, Kunming, Yunnan, China.

Basic Medical Laboratory, People's Liberation Army Joint Logistic Support Force 920th Hospital, Kunming, Yunnan, China.

出版信息

J Nanobiotechnology. 2024 Apr 12;22(1):177. doi: 10.1186/s12951-024-02451-2.

DOI:10.1186/s12951-024-02451-2
PMID:38609995
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11015550/
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.

摘要

目前临床修复软骨缺损的一线治疗方法是微骨折（MF）的创建，以刺激间充质干细胞（MSCs）的释放；然而，这种方法有很多局限性。最近的研究发现，MSC 衍生的细胞外囊泡（MSC-EVs）在组织再生中发挥重要作用。本研究旨在验证 MSC-EVs 是否促进 MF 介导的软骨损伤修复，并探讨修复机制。体外实验表明，人脐带华通氏胶 MSC-EVs（hWJMSC-EVs）促进软骨细胞活力以及骨髓来源 MSCs 的增殖和分化能力。这主要是因为 hWJMSC-EVs 携带整合素β-1（ITGB1），软骨和骨髓来源的 MSCs 在吸收 EVs 后过度表达 ITGB1，从而激活转化生长因子-β/Smad2/3 轴。在兔膝关节软骨缺损修复模型中，将不同浓度的 hWJMSC-EVs 注入关节腔，结果表明 50μg/ml 的浓度显著改善 MF 手术后透明软骨的形成。提取再生软骨发现，ITGB1、转化生长因子-β 和 Smad2/3 的变化与再生软骨的修复直接相关。综上所述，本研究表明 hWJMSC-EVs 促进 MF 手术后的软骨修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/720a/11015550/4bd5e44315c4/12951_2024_2451_Fig11_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/720a/11015550/ab647c038027/12951_2024_2451_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/720a/11015550/e152a886dcb0/12951_2024_2451_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/720a/11015550/74ca3f29f7dd/12951_2024_2451_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/720a/11015550/a39fb6a62551/12951_2024_2451_Fig9_HTML.jpg
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