Enhanced Collagen Type IV Based Differentiation of Embryonic Stem Cells Towards Flk‐1 Expressing Vascular Progenitors by the Wnt/β‐Catenin Synergist QS11

Abstract

AbstractMouse embryonic stem (mES) cells when plated onto collagen type IV in the presence of serum‐containing medium differentiate into a mixed cell population that contains low levels of Flk‐1 expressing vascular progenitor cells. When isolated and re‐plated onto collagen type IV, Flk‐1+ cells further differentiate into PECAM1+ endothelial and SMA+ mural cells. However, the low abundance and transient nature by which Flk‐1+ cells are generated during embryonic stem (ES) cell differentiation presents limitations in case large numbers of Flk‐1+ cells or its derivates are to be obtained. To optimize Flk‐1 progenitor induction from undifferentiated mES cells, the effects of QS11, a small organic molecule that synergistically activates canonical Wnt signalling, were investigated. In the presence of QS11 the percentage of Flk‐1+ cells in differentiating cultures of mES cells increases 1.5 fold. Furthermore, QS11 enhances cell proliferation in differentiating mES cells that results in a 2 fold increase in cell numbers when Flk‐1 induction is maximal. The combined effects of QS11 on differentiation and proliferation increase the efficiency by which Flk‐1 progenitors can be generated by approximately 300%, thereby providing a novel tool for vascular progenitor cell production for use in fundamental research and applications such as tissue engineering.