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.

Authors Lamandé SR, Ng ES, Cameron TL, Kung LHW, Sampurno L, Rowley L, Lilianty J, Patria YN, Stenta T, Hanssen E, Bell KM, Saxena R, Stok KS, Stanley EG, Elefanty AG, Bateman JF
Journal Proceedings of the National Academy of Sciences of the United States of America
Publication Date 2023 May 9;120(19):e2211510120
PubMed 37126720
PubMed Central PMC10175848
DOI 10.1073/pnas.2211510120

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