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Generation and characterization of cardiac valve endothelial-like cells from human pluripotent stem cells

Medicine and Health

Generation and characterization of cardiac valve endothelial-like cells from human pluripotent stem cells

L. Cheng, M. Xie, et al.

This groundbreaking study introduces a two-step, xeno-free method for generating valve endothelial-like cells from human pluripotent stem cells. The research, conducted by a team including LinXi Cheng and MingHui Xie, reveals the pivotal roles of TGFβ1 and BMP4 in cell differentiation, leading to superior performance on decellularized porcine aortic valve scaffolds. Discover how this advancement could reshape tissue engineering for heart valves!

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~3 min • Beginner • English
Abstract
The cardiac valvular endothelial cells (VECs) are an ideal cell source that could be used for making the valve organoids. However, few studies have been focused on the derivation of this important cell type. Here we describe a two-step chemically defined xeno-free method for generating VEC-like cells from human pluripotent stem cells (hPSCs). HPSCs were specified to KDR+/ISL1+ multipotent cardiac progenitors (CPCs), followed by differentiation into valve endothelial-like cells (VELs) via an intermediate endocardial cushion cell (ECC) type. Mechanistically, administration of TGFβ1 and BMP4 may specify VEC fate by activating the NOTCH/WNT signaling pathways and previously unidentified targets such as ATF3 and KLF family of transcription factors. When seeded onto the surface of the de-cellularized porcine aortic valve (DCV) matrix scaffolds, hPSC-derived VELs exhibit superior proliferative and clonogenic potential than the primary VECs and human aortic endothelial cells (HAEC). Our results show that hPSC-derived valvular cells could be efficiently generated from hPSCs, which might be used as seed cells for construction of valve organoids or next generation tissue engineered heart valves.
Publisher
Communications Biology
Published On
Sep 06, 2021
Authors
LinXi Cheng, MingHui Xie, WeiHua Qiao, Yu Song, YanYong Zhang, YingChao Geng, WeiLin Xu, Lin Wang, Zheng Wang, Kai Huang, NianGuo Dong, YuHua Sun
Tags
valve endothelial-like cells
human pluripotent stem cells
cardiac progenitors
TGFβ1
BMP4
tissue engineering
heart valves
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