Investigation of human vascular development and aging using human ES/iPS cells

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We succeeded in inducing iPS cells to differentiate into vascular endothelial cells (ECs) and mural cells (MCs), which we were able to isolate. We also established a feeder- and serum-free method that enables us to more efficiently induce ECs. Human ES-derived ECs (ESECs) and iPS-derived ECs (iPSECs) had a greater potential for wound re-endothelialization and tube formation than human adult ECs (HAECs) in vitro. Next we carried out a gene expression analysis of these three types of ECs using gene chip technology. The expression level of Sirt1, an aging-related gene that encodes a NAD-dependent histone deacetylase, was higher in ESECs/iPSECs than in HAECs. When Sirt1 activity was knocked down by siRNA or inhibited by a specific Sirt1 antagonist, the aforementioned differences in the cellular functionality were abolished, which suggests that differences in Sirt1 activity contribute to the observed differences in the cellular functionality.