Jiang Shuangpeng, Tian Guangzhao, Yang Zhen, Gao Xiang, Wang Fuxin, Li Juntan, Tian Zhuang, Huang Bo, Wei Fu, Sang Xinyu, Shao Liuqi, Zhou Jian, Wang Zhenyong, Liu Shuyun, Sui Xiang, Guo Quanyi, Guo Weimin, Li Xu
Department of Orthopedics, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning Province, China.
Institute of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Bioact Mater. 2021 Feb 13;6(9):2711-2728. doi: 10.1016/j.bioactmat.2021.01.031. eCollection 2021 Sep.
Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.
关节软骨缺损修复是一个长期困扰临床医生的问题。尽管间充质干细胞（MSCs）具有再生关节软骨的潜力，但它们也有许多局限性。最近的研究发现，MSC来源的外泌体（MSC-Exos）在组织再生中发挥着重要作用。本研究的目的是验证MSC-Exos是否能增强脱细胞软骨细胞外基质（ACECM）支架的修复效果，并探讨其潜在机制。体外实验结果表明，人脐带华通氏胶MSC-Exos（hWJMSC-Exos）可促进骨髓来源的间充质干细胞（BMSCs）的迁移和增殖以及软骨细胞的增殖。我们还发现hWJMSC-Exos可促进巨噬细胞向M2表型极化。兔膝关节骨软骨缺损修复模型的结果证实，hWJMSC-Exos可增强ACECM支架的效果并促进骨软骨再生。我们使用大鼠膝关节骨软骨缺损模型证明hWJMSC-Exos可调节关节腔的微环境。这种作用主要表现为促进巨噬细胞向M2表型极化并抑制炎症反应，这可能是骨软骨再生的促进因素。此外，微小RNA（miRNA）测序证实hWJMSC-Exos含有许多可促进透明软骨再生的miRNA。我们通过靶基因预测和通路富集分析进一步阐明了hWJMSC-Exos在骨软骨再生中的作用。总之，本研究证实hWJMSC-Exos可增强ACECM支架的效果并促进骨软骨再生。
