Chondrogenic differentiation in vitro of hiPSCs activates pathways engaged in limb development

Abstract

Human induced pluripotent stem cells (hiPSCs) are a true breakthrough in regenerative medicine with the potential to successfully treat many diseases, including orthopedic lesions, that are unresponsive to current treatments. However, chondrogenic differentiation in vitro is a poorly understood process and more research is needed. In this study, we compared the gene expression profile of chondrocyte-like cells differentiated from hiPSCs via monolayer culture (ChiPS) to the profile of mature chondrocytes and to a line of hiPSCs created by our group (GPCCi001-A). Our results indicate that ChiPS possess features of early chondrocytes. This finding was confirmed by RT-qPCR analysis, which demonstrated that the ALX1, EYA1, HOXB6, HOXC11, HOXD13 and RARB genes were more highly expressed in the ChiPS versus both GPCCi001-A cells and adult chondrocytes. These findings provide a better understanding the processes directing the cell fate of hiPSCs during chondrogenesis in vitro. Moreover, our group has created a potentially unlimited source of early chondrocytes that may prove useful in future clinical practice.