Defining Minimum Essential Factors to Derive Highly Pure Human Endothelial Cells from iPS/ES Cells in an Animal Substance-Free System

Abstract

It is desirable to obtain unlimited supplies of endothelial cells for research and therapeutics However current methods of deriving endothelial cells from humans suffer from issues such as limited supplies contamination from animal substances and lengthy/complicated procedures In this article we developed a way to differentiate human iPS and ES cells to highly pure endothelial cells in 5 days The chemically defined system is robust easy to perform and free of animal substances Using the system we verified that combined TGFβ and canonical Wnt agonists are essential and sufficient for iPS/ES cell-to-mesoderm transition Besides VEGF-KDR signaling alone is required for endothelial formation at high density while supplementation with FGF allows for colonial endothelial differentiation Finally anti-adsorptive agents could enrich the endothelial output by allowing selective attachment of the endothelial precursors The system was validated to work on multiple iPS/ES cells lines to produce endothelial cells capable of forming capillary-like structures in vitro and integrating into host vasculature in vivo In sum the simple yet robust differentiation system permits the unlimited supply of human endothelial cells The defined and animal substance-free nature of the system is compatible with clinical applications and characterization of endothelial differentiation in an unbiased manner

Date of Award	2016 Oct 4
Original language	English
Supervisor	Po-Min Chiang (Supervisor)