Venous and Arterial Endothelial Cells from Human Umbilical Cords: Potential Cell Sources for Cardiovascular Research.

Skadi Lau,Manfred Gossen,Andreas Lendlein,Friedrich Jung

doi:10.3390/ijms22020978

Abstract

Although cardiovascular devices are mostly implanted in arteries or to replace arteries, in vitro studies on implant endothelialization are commonly performed with human umbilical cord-derived venous endothelial cells (HUVEC). In light of considerable differences, both morphologically and functionally, between arterial and venous endothelial cells, we here compare HUVEC and human umbilical cord-derived arterial endothelial cells (HUAEC) regarding their equivalence as an endothelial cell in vitro model for cardiovascular research. No differences were found in either for the tested parameters. The metabolic activity and lactate dehydrogenase, an indicator for the membrane integrity, slightly decreased over seven days of cultivation upon normalization to the cell number. The amount of secreted nitrite and nitrate, as well as prostacyclin per cell, also decreased slightly over time. Thromboxane B2 was secreted in constant amounts per cell at all time points. The Von Willebrand factor remained mainly intracellularly up to seven days of cultivation. In contrast, collagen and laminin were secreted into the extracellular space with increasing cell density. Based on these results one might argue that both cell types are equally suited for cardiovascular research. However, future studies should investigate further cell functionalities, and whether arterial endothelial cells from implantation-relevant areas, such as coronary arteries in the heart, are superior to umbilical cord-derived endothelial cells.

Highlights

Cardiovascular diseases, such as coronary artery disease affecting the heart, stroke affecting the brain, peripheral artery disease affecting the extremities, and aortic disease affecting all inner organs, represent the number one cause of death worldwide [1]
While few of the endothelial cells (EC) showed the characteristic morphology at day 2 of cultivation, rather displaying a roundish to elongated shape, they phenotypically shifted towards a typical cobblestone-like pattern with increasing cell density at day 4 and 7
The present study did not detect any notable differences between Human umbilical vein endothelial cells (HUVEC) and human umbilical cord-derived arterial endothelial cells (HUAEC) regarding selected EC-specific properties necessary for the successful endothelialization of cardiovascular implants, including proliferation, and secretion of vasoactive substances and extracellular matrix proteins

Summary

Introduction

Cardiovascular diseases, such as coronary artery disease affecting the heart, stroke affecting the brain, peripheral artery disease affecting the extremities, and aortic disease affecting all inner organs, represent the number one cause of death worldwide [1]. Arterial EC are typically thicker, and exhibit a rather long and ellipsoidal morphology compared to shorter and wider venous endothelial cells. This difference is probably due to different shear stress levels, which are higher in arteries than in veins (reviewed in [5,6]). The formation of new blood vessels from existing ones, referred to as angiogenesis, occurs in both arteries and veins. This process is supported by vascular endothelial growth factor, but differentially inhibited by endogenous opioid growth factor [9]

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Conclusion