Abstract
Background： Cartilage tissue engineering is a promising option for repairing cartilage defects caused by trauma, inflammation and osteoarthritis, although harvesting a large number of seeding cells with stable phenotypes remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles secreted by mesenchymal stem cells may play a major role in cell-cell and tissue-tissue communication by transporting various RNAs and proteins in mesenchymal stem cell-based therapy. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived extracellular vesicles (EVs) on CSPCs proliferation and differentiation. Methods: The characteristics of ADSCs-derived EVs were identified by and flow cytometric analysis. Proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. The effect of ADSC-derived EVs on CSPCs were evaluated in alginate hydrogel culture, and SEM, histological staining, biochemical and biomechanical analysis were performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture. Results: The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40–1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induced CSPCs to produce significantly more cartilage matrix and proteoglycan. Conclusions: The present study indicated that hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.
3-Dimensional porous nanocomposite scaffolds based on cellulose nanofibers for cartilage tissue engineering: tailoring of porosity and mechanical performance
