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:
目前临床上修复软骨缺损的一线治疗方法是制造微骨折(MF)以刺激间充质干细胞(MSCs)的释放;然而,这种方法有许多局限性。最近的研究发现,MSC来源的细胞外囊泡(MSC-EV)在组织再生中起重要作用。本研究旨在验证MSC-EV是否促进MFs介导的软骨损伤修复,并探讨其修复机制。体外实验表明,人脐带Wharton的果冻MSC-EV(hWJMSC-EV)促进软骨细胞的活力和骨髓间充质干细胞的增殖和分化能力。这主要是因为hWJMSC-EV携带整合素β-1(ITGB1),软骨和骨髓来源的MSCs在吸收电动汽车后过度表达ITGB1,从而激活转化生长因子-β/Smad2/3轴。兔膝关节骨软骨缺损修复模型,向关节腔内注射不同浓度的hWJMSC-EV表明,50µg/ml的浓度可显着改善MF手术后透明软骨的形成.提取再生软骨显示ITGB1、转化生长因子-β、Smad2/3与再生软骨的修复成正比。总之,这项研究表明,hWJMSC-EV促进MF手术后的软骨修复。