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

Katsutsugu Umeda, Jiangang Zhao, Paul J Simmons, Edouard G Stanley, Andrew G Elefanty, Naoki Nakayama

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    52 Citations (Scopus)

    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 KDR(-)PDGFRalpha(+) 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/TGFbeta signaling controller. Isolated (GFP(+))KDR(-)PDGFRalpha(+) mesoderm cells were sensitive to sequential addition of the three chondrogenic factors PDGF, TGFbeta 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 KDR(-)PDGFRalpha(+ )paraxial mesoderm-like cells have potential in engineered cartilage formation and cartilage repair.
    Original languageEnglish
    Pages (from-to)1 - 11
    Number of pages11
    JournalScientific Reports
    Volume2
    Issue numberArt. No.: 455
    DOIs
    Publication statusPublished - 2012

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