Latest Studies using Microvascular Endothelial Cells

Microvessels are the smallest blood vessels within the vasculature and include capillaries, arterioles, and venules. Microvessels play a significant role in cancer, as they can indicate neoangiogenesis, the growth of new blood vessels. Induction of angiogenesis is a hallmark of cancer, and this increased blood supply helps feed tumors and facilitate their growth. In fact, microvessel density is used in the clinic to evaluate tumor angiogenesis. Angiogenesis is induced by vascular endothelial growth factor (VEGF), which bind its receptor on endothelial cells and stimulates their growth and migration.

Microvessels, like all vasculature, contain endothelial cells, which line the vessel and interact with blood. Microvascular endothelial cells also play an active role in vessel homeostasis, and when disrupted, may contribute to disease. In particular, endothelial cells can undergo a process called endothelial-to-mesenchymal transition, through which they lose their endothelial identity, transdifferentiating into mesenchymal cells and assuming new roles within a tissue.

Recent Studies Using Lifeline® Microvascular Endothelial Cells

Traumatic heterotopic ossification (HO) occurs when bone forms ectopically in soft tissues following injury to those tissues. How this occurs and the cell-of-origin of these ectopic bone growths have been a source of study in recent years. In a study this year, Sun et al. investigated the mechanisms behind traumatic HO development and the cell-of-origin that drives this process. They found that human traumatic HO tissues expressed endothelial and osteoblast markers, suggesting that HO is derived from endothelial cells that underwent an endothelial to mesenchymal transition (EndMT) to become osteoblasts. Additionally, they found that miR-630 was downregulated in HO patient tissue, identifying it as a target of interest for investigating the mechanisms of HO.

The researchers used Lifeline® human dermal microvascular endothelial cells (HD-MVECs) to induce EndMT and found that miR-630 decreases following EndMT, and the resultant mesenchymal cells form HO in a mouse model. The group also found that miR-630 likely regulates HO following EndMT through Slug, which decreases following miR-630 overexpression and can induce EndMT when overexpressed. Finally, the researchers demonstrate that miR-630 can be detected in patient serum and is downregulated at early stages of traumatic HO. Together, the results of this study identify endothelial cells as the cells-of-origin for traumatic HO, illustrate that miR-630 downregulation may serve as a potential biomarker for early traumatic HO, and demonstrate that decreased miR-630 levels result in EndMT, likely through subsequent upregulation of Slug.

Vascular endothelial growth factor (VEGF) activates endothelial cells by binding its receptors VEGFR-1 and VEGFR-2. VEGFR-1, or Flt-1, has both membrane-bound and soluble forms, generated by alternative mRNA polyadenylation. In a recent study, Ikeda et al. investigated the mechanisms by which this alternative polyadenylation is regulated using Lifeline® human microvascular endothelial cells (HMVECs). The group found that the heterogeneous ribonucleoprotein (hnRNP) D could bind the Flt-1 pre-mRNA and induce alternative polyadenylation of Flt-1, increasing the amount of soluble Flt-1 (sFLt-1). They demonstrate that this involves Arginine 277 and arginine methylation. They argue that loss of arginine methylation enables production of the alternative sFlt-1, and this process is hindered upon active arginine methylation.  The results of their study could have implications for activation of endothelial cells and induction of angiogenesis.

Lifeline® Microvascular Endothelial Cells

Lifeline® offers three types of microvascular endothelial cells:

• Dermal-derived microvascular endothelial cells-Neonatal
• Dermal-derived microvascular endothelial cells-Adult
• Lung-derived microvascular endothelial cells

Lifeline® microvascular endothelial cells are optimized for growth in VascuLife^® EnGS-Mv Medium and VascuLife^® VEGF-Mv Medium.

Tell us how you are using our Endothelial Cells to answer your research questions and your study could be featured here on our blog!