Electrical stimulation induces direct reprogramming of human dermal fibroblasts into hyaline chondrogenic cells

Abstract

The repair of articular cartilage needs a sufficient number of chondrocytes to replace the defect tissue. Direct reprogramming of fibroblasts into chondrocytes can provide a sufficient number of chondrocytes because fibroblasts can be expanded efficiently. Herein, we demonstrate for the first time that electrical stimulation can drive direct reprogramming of human dermal fibroblasts (HDFs) into hyaline chondrogenic cells. Our results shows that electrical stimulation drives condensation of HDFs and then enhances expression levels of chondrogenic markers, such as type II collagen, aggrecan, and Sox9, and decreases type I collagen levels without the addition of exogenous growth factors or gene transduction. Electrical stimulation-directly reprogrammed chondrogenic cells showed the normal karyotype. It was also found that electrical stimulation increased the secretion levels of TGF-beta1, PDGF-AA, and IGFBP-2, 3. These findings may contribute to not only novel approach of direct reprogramming but also cell therapy for cartilage regeneration.

Keywords: Direct reprogramming; Electrical stimulation; Human dermal fibroblasts; Hyaline chondrogenic cells.