Modeling human skeletal development using human pluripotent stem cells

Chondrocytes and osteoblasts differentiated from induced pluripotent stem cells (iPSCs) will provide insights into skeletal development and genetic skeletal disorders and will generate cells for regenerative medicine applications. Here, we describe a method that directs iPSC-derived sclerotome to chondroprogenitors in 3D pellet culture then to articular chondrocytes or, alternatively, along the growth plate cartilage pathway to become hypertrophic chondrocytes that can transition to osteoblasts. Osteogenic organoids deposit and mineralize a collagen I extracellular matrix (ECM), mirroring in vivo endochondral bone formation. We have identified gene expression signatures at key developmental stages including chondrocyte maturation, hypertrophy, and transition to osteoblasts and show that this system can be used to model genetic cartilage and bone disorders.

Automated summary

Researchers have developed a method to direct iPSC-derived sclerotome to differentiate into chondroprogenitors or articular chondrocytes, and further transition into hypertrophic chondrocytes and osteoblasts. The system can be used to model genetic skeletal disorders and generate cells for regenerative medicine applications, mimicking in vivo bone formation.