Background: Mesenchymal stem cells (MSCs) offer a promising avenue for cartilage regeneration; however, their therapeutic efficacy requires substantial improvement. Cell priming using electrical stimulation (ES) is a promising approach to augmenting the therapeutic potential of MSCs and has shown potential for various regenerative applications. This study aimed to promote the ES-mediated chondrogenic differentiation of human MSCs and facilitate the repair of injured articular cartilage. Methods: MSCs were subjected to ES under various conditions (e.g., voltage, frequency, and number of repetitions) to enhance their capability of chondrogenesis and cartilage regeneration. Chondrogenic differentiation of electrically primed MSCs (epMSCs) was assessed based on gene expression and sulfated glycosaminoglycan production, and epMSCs with hyaluronic acid were transplanted into a rat osteochondral defect model. Transcriptomic analysis was performed to determine changes in gene expression by ES. Results: epMSCs exhibited significantly increased chondrogenic gene expression and sulfated glycosaminoglycan production compared with those in unstimulated controls. Macroscopic and histological results showed that in vivo epMSC transplantation considerably enhanced cartilage regeneration. Furthermore, ES markedly altered the expression of numerous genes of MSCs, including those associated with the extracellular matrix, the Wnt signaling pathway, and cartilage development. Conclusion: ES can effectively prime MSCs to improve articular cartilage repair, offering a promising strategy for enhancing the efficacy of various MSC-based therapies.
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