Simple and Highly Efficient Method for Production of Endothelial Cells from Human Embryonic Stem Cells

Abstract

Endothelial cells derived from human embryonic stem cells (hESC-ECs) hold much promise as a valuable tool for basic vascular research and for medical application such as cell transplantation or regenerative medicine. Here we have developed an efficient approach for the production of hESC-ECs. Using a differentiation method consisting of a stepwise combination of treatment with glycogen synthase kinase-3β (GSK-3β) inhibitor and culturing in vascular endothelial growth factor (VEGF)-supplemented medium, hESC-ECs are induced in 5 days with about 20% efficiency. These cells express vascular endothelial cadherin (VE-cadherin), VEGF receptor-2 (VEGFR-2), CD34, and platelet endothelial cell adhesion molecule-1 (PECAM-1). These hESC-ECs can then be isolated with 95% purity using a magnetic sorting system, and expanded to more than 100-fold within a month. The hESC-ECs thus produced exhibit the endothelial morphological characteristics and specific functions such as capillary tube formation and acetylated low-density lipoprotein uptake. We propose that our methodology is useful for efficient and large-scale production of hESC-ECs.