[HTML][HTML] Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells

K Umeda, J Zhao, P Simmons, E Stanley, A Elefanty… - Scientific reports, 2012 - nature.com
K Umeda, J Zhao, P Simmons, E Stanley, A Elefanty, N Nakayama
Scientific reports, 2012nature.com
Directed specification and prospective isolation of chondrogenic paraxial mesoderm
progeny from human pluripotent stem (PS) cells have not yet been achieved. Here we report
the successful generation of KDR− PDGFRα+ progeny expressing paraxial mesoderm
genes and the mesendoderm reporter MIXL1-GFP in a chemically defined medium
containing the canonical WNT signaling activator, BMP-inhibitor and the Nodal/Activin/TGFβ
signaling controller. Isolated (GFP+) KDR− PDGFRα+ mesoderm cells were sensitive to …
Abstract
Directed specification and prospective isolation of chondrogenic paraxial mesoderm progeny from human pluripotent stem (PS) cells have not yet been achieved. Here we report the successful generation of KDRPDGFRα+ progeny expressing paraxial mesoderm genes and the mesendoderm reporter MIXL1-GFP in a chemically defined medium containing the canonical WNT signaling activator, BMP-inhibitor and the Nodal/Activin/TGFβ signaling controller. Isolated (GFP+)KDRPDGFRα+ mesoderm cells were sensitive to sequential addition of the three chondrogenic factors PDGF, TGFβ and BMP. Under these conditions, the cells showed robust chondrogenic activity in micromass culture and generated a hyaline-like translucent cartilage particle in serum-free medium. In contrast, both STRO1+ mesenchymal stem/stromal cells from adult human marrow and mesenchymal cells spontaneously arising from hPS cells showed a relatively weaker chondrogenic response in vitro and formed more of the fibrotic cartilage particles. Thus, hPS cell-derived KDRPDGFRα+paraxial mesoderm-like cells have potential in engineered cartilage formation and cartilage repair.
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