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Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have great potentials for cell-based therapies based on their abundant potentials of self renewal and differentiation into all cell lineages (1,2). A serum-free ES cell differentiation system has an advantage for clinical applications because it can efficiently induce a specific cell lineage, and can avoid the risk of viral or prion infection by biomaterials. This study was initiated to examine how to efficiently induce paraxial mesodermal progenitor cells from ES cells in serum-free cultures. BMP4 acted as a key factor to promote the primitive streak-type mesoderm in both mouse development and ES cell differentiation in culture. Many lateral mesodermal derivatives such as hematopoietic cells, endothelial cells and cardiomyocytes, and intermediate mesoderm derivatives such as renal progenitors have been induced by BMP4 stimulation. However, differentiation of paraxial mesodermal cells from ES cells in serum-free culture has remained elusive. In this study, we developed a simple culture system with BMP4 and lithium chloride (LiCl) in serum-free conditions to promote two types of paraxial mesodermal progenitors, osteochondrogenic progenitors, and myogenic progenitors, which were identified using the paraxial mesodermal marker PDGFR-α.

Specific Serum-free Conditions can Differentiate Mouse Embryonic Stem Cells into Osteochondrogenic and Myogenic Progenitors.