Journal
BIOACTIVE MATERIALS
Volume 6, Issue 9, Pages 2711-2728Publisher
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.01.031
Keywords
Articular cartilage; Regeneration; Tissue engineering; Mesenchymal stem cells; Exosomes
Funding
- National Key RAMP
- D Program of China [2019 YFA 0110600]
- National Natural Science Foundation of China [81772319]
- Scientific Research Funding Project of Education Department of Liaoning Province [JC2019001]
- China Postdoctoral Science Foundation [2020M681010]
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This study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. The promoting effect may be related to the polarization of macrophages and inhibition of inflammatory response by hWJMSC-Exos. Additionally, hWJMSC-Exos contain miRNAs that can promote hyaline cartilage regeneration.
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.
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