Articular chondrocyte-derived extracellular vesicles promote cartilage differentiation of human umbilical cord mesenchymal stem cells by activation of autophagy

Journal of Nanobiotechnology

Danyan Ye¹  Lujun Yang²  Bo Zhu³  Li Zheng³  Guohua Yan⁴  Mingwei He⁴  Peian Cai⁴  Jinmin Zhao⁵  Ke Ma⁶  Zetao Wang⁷ 

[1] Department of Burns and Plastic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China;Research Centre for Translational Medicine, Shantou University Medical College, Shantou, China;Department of Burns and Plastic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China;Research Centre for Translational Medicine, Shantou University Medical College, Shantou, China;Pharmaceutical College, Guangxi Medical University, Nanning, China;Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;International Joint Laboratory of Ministry of Education for Regeneration of Bone and Soft Tissues, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Plastic & Cosmetic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;Pharmaceutical College, Guangxi Medical University, Nanning, China;

关键词: Autophagy;    Chondrocytes;    Chondrogenesis;    Extracellular vesicles;    Human umbilical cord mesenchymal stem cells;   

DOI  :  10.1186/s12951-020-00708-0

来源: Springer

【 摘 要 】

BackgroundUmbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported.ResultsWe successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy.ConclusionsC-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

【 授权许可】

CC BY