Significance
Several studies have examined the stiffness-induced cell fate from pluripotent stem cells during the stage of mesoderm cell differentiation. This is the first research that rigorously examines the effect of substrate stiffness on human valve endothelial-like cells differentiation from cardiac progenitor cells. We found that the medium stiffness can increase the differentiation efficiency of h-iVECs from 40% to about 60%, and this process was regulated by the WNT/CaN signaling pathway through the activation of WNT5a. Substrate stiffness not only increases the differentiation efficiency of h-iVECs, but also improves its cellular functions such as low-density lipoprotein uptake and NO release. This study emphasizes the importance of using substrate stiffness to accomplish a more specific and mature differentiation of h-iVECs.
Statement of significance
Several studies have examined the stiffness-induced cell fate from pluripotent stem cells during the stage of mesoderm cell differentiation. This is the first research that rigorously examines the effect of substrate stiffness on human valve endothelial-like cells differentiation from cardiac progenitor cells. We found that the medium stiffness can increase the differentiation efficiency of h-iVECs from 40% to about 60%, and this process was regulated by the WNT/CaN signaling pathway through the activation of WNT5a. Substrate stiffness not only increases the differentiation efficiency of h-iVECs, but also improves its cellular functions such as low-density lipoprotein uptake and NO release. This study emphasizes the importance of using substrate stiffness to accomplish a more specific and mature differentiation of h-iVECs.