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

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(-)PDGFR?(+) 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/TGF? signaling controller. Isolated (GFP(+))KDR(-)PDGFR?(+) mesoderm cells were sensitive to sequential addition of the three chondrogenic factors PDGF, TGF? 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(-)PDGFR?(+ )paraxial mesoderm-like cells have potential in engineered cartilage formation and cartilage repair.

SUBMITTER: Umeda K 

PROVIDER: S-EPMC3374161 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature