Affiliation:
1. Shanghai Key Laboratory of Tissue Engineering, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
2. Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27101, USA
Abstract
Repairing cartilage defects represents a significant clinical challenge. While adipose-derived stem cell (ADSC)-based strategies hold promise for cartilage regeneration, their inherent chondrogenic potential is limited. Extracellular vesicles (EVs) derived from chondrocytes (CC-EVs) have shown potential in enhancing chondrogenesis, but their role in promoting chondrogenic differentiation of ADSCs remains poorly understood. Moreover, the clinical application of EVs faces limitations due to insufficient quantities for in vivo use, necessitating the development of effective methods for extracting significant amounts of CC-EVs. Our previous study demonstrated that low-intensity ultrasound (LIUS) stimulation enhances EV secretion from mesenchymal stem cells. Here, we identified a specific LIUS parameter for chondrocytes that increased EV secretion by 16-fold. CC-EVs were found to enhance cell activity, proliferation, migration, and 21-day chondrogenic differentiation of ADSCs in vitro, while EVs secreted by chondrocytes following LIUS stimulation (US-CC-EVs) exhibited superior efficacy. miRNA-seq revealed that US-CC-EVs were enriched in cartilage-regeneration-related miRNAs, contributing to chondrogenesis in various biological processes. In conclusion, we found that CC-EVs can enhance the chondrogenesis of ADSCs in vitro. In addition, our study introduces ultrasound-driven healing as an innovative method to enhance the quantity and quality of CC-EVs, meeting clinical demand and addressing the limited chondrogenic potential of ADSCs. The ultrasound-driven healing unleashes the potential of CC-EVs for chondrogenesis possibly through the enrichment of cartilage-regeneration-associated miRNAs in EVs, suggesting their potential role in cartilage reconstruction. These findings hold promise for advancing cartilage regeneration strategies and may pave the way for novel therapeutic interventions in regenerative medicine.
Funder
the Industrial Support Fund of Huangpu District
Plastic Surgery of Shanghai Key Clinical Project
Shanghai Sailing program
the National Natural Science Foundation of China
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)