Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells

Summary Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization.
Highlights • Side-by-side comparison of hiPSC and primary ECs in standardized assays • Barrier function and inflammatory responses highly consistent among hiPSC-ECs • hiPSC-ECs on differentiation day 10 were similar across independent batches and lines • hiPSC-ECs are more limited in stromal cell requirements than primary ECs
In this article, Orlova and colleagues show that hiPSC-ECs have similar features to primary ECs but also show some differences. hiPSC-ECs exhibited higher barrier function, lower expression of pro-inflammatory adhesive receptors, and more stringent stromal cell requirements. Importantly, healthy control CD31+ hiPSC-ECs showed high consistency between different batches and lines, forming a good basis for disease modeling applications.