IMPACT OF BIOPHYSICAL CUES ON THE FUNCTIONAL MATURITY OF PLURIPOTENT STEM CELL DERIVED ENDOTHELIAL CELLS INTO ARTERIAL AND VENOUS SUBTYPES

Abstract

Pluripotent stem cell derived endothelial cells (PSC-EC) are an upcoming alternate source for cardio-vascular clinical applications. However, PSC-ECs are functionally heterogeneous and functionally immature compared to primary ECs. Hence, this study aims to functionally mature them to either arterial or venous subtype using biophysical cues. Arterial and venous ECs reside in different microenvironments with varying basement membrane architecture and different shear stress. Thus, this study incorporated a Multi Architectural (MARC) chip to study the effect of substrate topography and a multiplex microfluidic device to study the effect of shear on the functional maturity of PSC-EC into the two EC subtypes. We established that gratings and micro-lenses positively enhanced the arterial phenotype of PSC-ECs. Whereas, a low shear stress ≥ 3.8dyne/cm2 for 40-hours supported an arterial phenotype in PSC-ECs. Both biophysical cues overall had a positive influence towards arterial phenotype.