23 Jul HUMAN EMBRYONIC STEM CELL DERIVED MESODERM-LIKE EPITHELIUM TRANSITIONS TO MESENCHYMAL PROGENITOR CELLS
Abstract
Human embryonic stem cells (hESC) have the potential to produce all of the cells in the body. They are also able to self-renew indefinitely, sparking the hope they could be used as a source for large scale production of therapeutic cell lines. The present invention relates to a monolayer differentiation culture system that induces hESC (WA09 and BG0l) to form epithelial sheets with mesodermal gene expression patterns (BMP4, RUNXl, GAT A4). These E-cadherin+ CD90lovv cells then undergo apparent epithelial-mesenchymal transformation (EMT) for the derivation of mesenchymal progenitor cells (hES-MC) that by flow cytometry are negative for hematopoietic (CD34, CD45 and CD 133) and endothelial (CD31 and CD 146) markers, but positive for markers associated with mesenchymal stem cells (MSC) (CD73, CD90, CD105 and CD166). To determine their functionality, we tested their capacity to produce the three lineages commonly associated with MSC and found they could form osteogenic and chondrogenic, but not adipogenic lineages. The derived hES-MC were able to remodel and contract collagen I lattice constructs to an equivalent degree as keloid fibroblast control cells and were induced to express aSMA when exposed to TGF-ß1, but not PDGF-B. This data suggests the derived hES-MC cells are multipotent cells with potential uses in tissue engineering/regenerative medicine and for providing a highly reproducible cell source for adult-like progenitor cells.
Year: 2008
Country: WO
Doc No: 2008150498