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The Potential of Endothelial Cells in Tissue Engineering

For many years, mature human endothelial cells derived from human vasculature were the main tool used to research the biology of human endothelial cells. The early 1970s saw the successful isolation of ECs from human umbilical veins, which was of utmost significance and gave researchers around the world unheard-of access to human EC cultures. Consequently, endothelial cells quickly established themselves as a crucial tool in vascular biology research, dominating the area to this day.

In an attempt to integrate such pre-existing vascular networks, scientists have turned to primary endothelial cells (ECs), which have the innate ability to produce blood vessels. There is still general agreement that using ECs is essential to this effort and that bioengineering vascular networks are still a top focus in tissue engineering.

Human Umbilical Vein Microvascular Endothelial Cells (HUVECs)

Amongst all potential sources of endothelial cells, endothelial cells from umbilical cord veins are
successfully isolated and propagated in vitro during the early 1970s. Today, it has become a staple tool in vascular biology research. HUVECs continue to be the most popular human EC source in bioengineering to this day, despite the development of alternative stem/progenitor cell sources.

There are many causes for this ubiquity, but they all fundamentally arise from the fact that HUVECs have been researched for much longer than any other source of human ECs. HUVECs have become the favoured alternative for the development of procedures and standardised assays in vascular biology and angiogenesis research as a result of the knowledge that has been acquired about them over time. This knowledge has given HUVECs an advantage over competing options.

These cells are now widely available in both research labs and commercial businesses as a result of the development of common assays that need HUVECs. However, HUVECs have a short lifespan in culture, which limits the clinical applications they can be used for in an autologous setting. As a result, additional sources of ECs produced from pluripotent stem cells or progenitor cells may very well outperform HUVECs in the future.

Human Dermal Microvascular Endothelial Cells (HDMECs)

Besides HUVECs, one of the most studied sources of primary human endothelial cells is endothelial cells isolated from small-diameter veins of skin microvasculature. Some of the early proof of concept in vivo studies were carried out using HDMEs in SCID mice.

The HDMEC that line the blood arteries of the skin exhibit various skin-specific traits in addition to sharing characteristics with endothelial cells found in other parts of the body. They actively take part in a number of physiological activities, such as temperature regulation, hemostasis management, and wound healing. The endothelial lining of blood vessels exhibits excellent heterogeneity through signalling pathways that regulate cell proliferation, quiescence and apoptosis.

Human Endothelial Progenitors

Human Endothelial Progenitors obtained from circulating human peripheral blood are of widespread interest as a minimally invasive, more replicative cell source with the highest ability to form colonies in vitro. For therapeutic interventions, identifying endothelial progenitor cells in the blood is a promising way to obtain the required endothelium population without using any intrusive methods.

These cells are now more often referred to as endothelial colony-forming cells. Their first applications in bioengineering were reported by Wu in the year 2004. Additionally, it was demonstrated that endothelial progenitors were incorporated into the graft and formed perfused vasculature that linked up with arriving host vessels. This was one of the earliest in vivo examples of the application of human ECFCs to the bioengineering of the human vascular system.

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