Enhanced chondrogenesis from chondrocytes co-cultured on mesenchymal stromal cells: Implication for cartilage repair

Abstract

Cellular therapy based on chondrocytes implantation is the most widely used procedure for inducing cartilage regeneration. However, the dedifferentiation process that these cells suffer and their limited capacity of proliferation, when they are cultured in vitro, restrict their use in cellular therapy protocols. To investigate the capacity of mesenchymal stromal cells (MSCs) to promote chondrogenesis from chondrocytes or chondrons in 2D and 3D coculture systems. Murine chondrocytes and chondrons were cocultured with MSCs at different cell ratios (100/0, 50/50, 70/30, 0/100) in two-dimensional (2D) and three-dimensional (3D) culture systems. High proliferation of cells with chondrocyte morphology, enhanced GAG production and expression of cartilage genes (aggrecan, type II collagen, and SOX-9) were observed in chondrocytes/MSCs cocultures. In contrast, fibroblastoid cells, down-regulation of cartilage gene expression and reduction of GAG production were observed in chondrons/MSCs cocultures. Chondrocytes within cartilage lacunae and surrounded by extracellular matrix were observed in chondrocytes/MSC pellets. MSCs promote the proliferation of functional chondrocytes in 2D and 3D culture systems. Transplantation of chondrogenic construct based on MSCs and chondrocytes may constitute a potential treatment for inducing cartilage repair.