Cyclic Strain Promotes Expression and Vascular Tube Formation in iPSC-Derived Endothelial Cells.

INTRODUCTION

Induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have the potential for therapeutic application in several cardiovascular diseases. Mechanical strain is known to regulate EC behavior and stem cell differentiation and may play a role in directing EC differentiation of iPSCs. , a long non-coding RNA (lncRNA), is known to affect ECs in several mechanically relevant pathologies and may play a role in this process as well. Therefore, we investigated expression changes of resulting from mechanical stimulation during EC differentiation, as well as functional effects on EC tube formation.

METHODS

iPSCs were subjected to 5% cyclic mechanical strain during EC differentiation. RT-PCR and flow cytometry were used to assess changes in mesoderm differentiation and gene expression in the final ECs as a result of strain. Functional outcomes of mechanically differentiated ECs were assessed with a tube formation assay and changes in . was also overexpressed in human umbilical vein endothelial cells (HUVECs) to assess its role in non--expressing ECs.

RESULTS

Mechanical strain promoted mesoderm differentiation, marked by increased expression of brachyury 24 h after initiation of differentiation. Strain also increased expression of , , VE-cadherin, and in differentiated ECs. Strain-differentiated ECs formed tube networks with higher junction and endpoint density than statically-differentiated ECs. Overexpression of in HUVECs resulted in similar patterns of tube formation.

CONCLUSIONS

expression is increased by mechanical strain and promotes tube branching in iPSC-derived ECs.