Novel method to repair articular cartilage by direct reprograming of prechondrogenic mesenchymal stem cells

Abstract

Age-related cartilage loss is worsened by the limited regenerative capacity of chondrocytes. The role of cell-based therapies using mesenchymal stem cells is gaining interest. Adipose tissue-derived mesenchymal stem cells (ADSCs) are an attractive source to generate the optimal number of chondrocytes required to repair a cartilage defect and regenerate hyaline articular cartilage. Here, we report an outstanding technique to prepare chondrocytes for cartilage repair using canine ADSCs. We hypothesized that external electrical fields promote prechondrogenic condensation without requiring genetic modifications or exogenous factors. We analyzed the effect of electrical stimulation (ES) on the differentiation of ADSC micromass into chondrocytes. Highly compact structures were formed within 3 days of ES of canine ADSC micromass. The expression of type I collagen gene was abolished in these cells compared with that in control micromass cultures and monolayer cultures. We further found that ES enhanced the production of proteoglycan, a highly produced extracellular matrix component in chondrocytes. Additionally, single-cell RNA sequencing analysis showed that canine ADSC micromass undergoing ES developed a prechondrogenic cell aggregation, suggesting their metabolic conversion, biogenesis, and calcium ion change. Collectively, our findings demonstrate the capacity of ES to drive the chondrogenesis of ADSCs in the absence of exogenous factors and confirm its commercial potential as a budget-friendly therapy for the repair of cartilage defects.