Why Use HUVECs in my Research?
HUVECs, or human umbilical cord endothelial cells, are one of the most commonly used model systems to study vascular biology in vitro. As of the writing of this blog post, there were over 17,000 search results in PubMed for “HUVEC”.
But what are HUVECs and why are they such a popular in vitro model system?
HUVECs are endothelial cells isolated from the umbilical vein of the umbilical cord. During fetal development, the umbilical cord connects a fetus to the mother’s blood supply via the placenta. Blood is carried through the umbilical cord to the fetus through the umbilical vein, and away from the fetus through the two umbilical arteries. This blood supply supports fetal development, delivering the critical oxygen and nutrients the growing baby needs to survive.
Endothelial cells line the inside of blood vessels and are a critical component of vascular homeostasis. They are key players in angiogenesis, the process by which new blood vessels are formed from existing blood vessels. Additionally, endothelial cells are important in a number of vascular diseases, such as atherosclerosis, where their dysfunction plays a role in pathogenesis.
Endothelial cells are also of great interest in cancer research. In particular, the ability of tumors to induce angiogenesis has been considered a hallmark of cancer for the past decade. Tumors are experts at promoting their own growth and survival, and to do so, requires a healthy supply of oxygen- and nutrient-rich blood. As a mechanism of pathogenesis, solid tumors activate angiogenic processes to direct the formation of new blood vessels, enhancing the tumor blood supply to support the tumor’s needs. Thus, the development of novel therapeutic agents that target tumor angiogenesis is of great interest.
Given the role of endothelial cells in vascular homeostasis, vascular disease, and cancer pathogenesis, a reliable model system that closely mimics the vasculature in which to study endothelial cell dynamics is needed.
HUVECs were first isolated for in vitro culture in the early 1970s and since then, have been extensively used as a primary, non-immortalized cell system to study the vascular endothelium, largely due to the ease by which they are isolated and cultured.
HUVECs can be used in a number of standardized in vitro angiogenesis assays to study normal endothelial cell behavior or to evaluate how endothelial cells react to different stimuli or treatment with pro- and anti-angiogenic agents.
During the early phases of angiogenesis, endothelial cells proliferate and migrate toward a pro-angiogenic signal (e.g. vascular endothelial growth factor). HUVECs can be used in vitro to assess how different manipulations, such as treatment with an anti-angiogenic compound, affect endothelial migration and proliferation, and how this might regulate the subsequent formation of blood vessels.
HUVECs are also commonly used in tube formation assays, in which the ability of endothelial cells to form tubes—a process that occurs after endothelial proliferation and migration to the site of the pro-angiogenic stimulus—is assessed. In a tube formation assay, HUVECs are cultured on an extracellular matrix compound, such as Matrigel®, and their response to agents that disrupt or enhance this process can be evaluated. This assay is often used when testing anti-cancer therapeutic compounds that target tumor angiogenesis.
HUVECs have been used as an in vitro model system to study the vasculature for approximately 45 years, during which they have been instrumental in understanding the normal biology and dysfunction of the vascular endothelium. As technology and the ingenuity of researchers around the world advances our understanding of biology, HUVECs will undoubtedly continue to play their part.