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

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    Author
    Umeda, K; Zhao, J; Simmons, P; Stanley, E; Elefanty, A; Nakayama, N
    Date
    2012-06-13
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Stanley, Edouard; Elefanty, Andrew
    Affiliation
    Paediatrics (RCH)
    Metadata
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    Document Type
    Journal Article
    Citations
    Umeda, K., Zhao, J., Simmons, P., Stanley, E., Elefanty, A. & Nakayama, N. (2012). Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells. SCIENTIFIC REPORTS, 2 (1), https://doi.org/10.1038/srep00455.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256755
    DOI
    10.1038/srep00455
    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(-)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 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 KDR(-)PDGFRα(+ )paraxial mesoderm-like cells have potential in engineered cartilage formation and cartilage repair.

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