Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis

• DOI: 10.1186/s12951-021-01086-x
• Publication Date: 2021-10-26T18:02:42Z
• Authors: Shenglong Li; Jie Liu; Siyu Liu; Weijie Jiao; Xiaohong Wang
• Keywords: EVs-COS conjugates; Oligosaccharides; Mesenchymal Stem Cell Transplantation; Extracellular Vesicles; 03 medical and health sciences; Chondrocytes; Osteoarthritis; Medical technology; Animals; R855-855.5; Rats, Wistar; EVs; Cartilage injury repair; Cells, Cultured; Chitosan; Wound Healing; 0303 health sciences; Research; Chitosan oligosaccharides; Mesenchymal Stem Cells; Rats; Specific Pathogen-Free Organisms; Cartilage; Female; Transcriptome; TP248.13-248.65; Biotechnology

AbstractObjectivesThis study aimed to investigate the roles of adipose mesenchymal stem cell (AMSC)-derived extracellular vesicles (EVs) binding with chitosan oligosaccharides (COS) in cartilage injury, as well as the related mechanisms.ResultsIL-1β treatment significantly inhibited the viability and migration of chondrocytes and enhanced cell apoptosis (P < 0.05), while chitosan oligosaccharides and extracellular vesicles-chitosan oligosaccharide conjugates (EVs-COS/EVs-COS conjugates) reversed the changes induced by IL-1β (P < 0.05), and the effects of extracellular vesicles-chitosan oligosaccharide conjugates were better than those of chitosan oligosaccharides (P < 0.05). After cartilage damage, IL-1β, OPN, and p53 were significantly upregulated, COL1A1, COL2A1, OCN, RUNX2, p-Akt/Akt, PI3K, c-Myc, and Bcl2 were markedly downregulated, and extracellular vesicles-chitosan oligosaccharide conjugates reversed the expression induced by cartilage injury. Through sequencing, 760 differentially expressed genes (DEGs) clustered into four expression patterns were associated with negative regulation of the canonical Wnt, PI3K-Akt, AMPK, and MAPK signaling pathways.ConclusionExtracellular vesicles-chitosan oligosaccharide conjugates may serve as a new cell-free biomaterial to facilitate cartilage injury repair and improve osteoarthritis.Graphical Abstract