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

• Published in: Journal of nanobiotechnology Vol. 19; no. 1; pp. 343 - 19
• Main Authors: Li, Shenglong, Liu, Jie, Liu, Siyu, Jiao, Weijie, Wang, Xiaohong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.10.2021; BioMed Central; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; Adipose tissues; AKT protein; Animals; Apoptosis; Arthritis; Articular cartilage; Biological products; Biomaterials; Biomedical materials; Bones; c-Myc protein; Care and treatment; Cartilage; Cartilage - drug effects; Cartilage - injuries; Cartilage - metabolism; Cartilage diseases; Cartilage injury repair; Cbfa-1 protein; Cell organelles; Cells, Cultured; Chitin; Chitosan; Chitosan - chemistry; Chitosan - pharmacology; Chitosan oligosaccharides; Chondrocytes; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Collagen; Collagen (type I); Conjugates; Drugs; EVs; EVs-COS conjugates; Extracellular vesicles; Extracellular Vesicles - chemistry; Female; Health aspects; Hydroxyapatite; IL-1β; Injuries; MAP kinase; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Morphology; Myc protein; Nanocomposites; Oligosaccharides; Oligosaccharides - chemistry; Oligosaccharides - pharmacology; Osteoarthritis; Osteoarthritis - metabolism; p53 Protein; Physiological aspects; Rats; Rats, Wistar; Repair; Specific Pathogen-Free Organisms; Stem cell transplantation; Stem cells; Testing; Tissue engineering; Transcriptome - genetics; Vesicles; Wnt protein; Wound healing; Wound Healing - drug effects; China; Chitosan oligosaccharides; EVs-COS conjugates; EVs; Cartilage injury repair; Osteoarthritis
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-021-01086-x

This 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. IL-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. Extracellular vesicles-chitosan oligosaccharide conjugates may serve as a new cell-free biomaterial to facilitate cartilage injury repair and improve osteoarthritis.