Abstract
Angiogenesis occurs during both physiological and pathological processes. In this study, a microfluidic chip for the development of angiogenesis was utilized to assess angiogenic sprouting and functional vessel formation. We also found that vascular endothelial growth factor (VEGF) was a determinant of the initiation of vascular sprouts, while the direction of these sprouts was greatly influenced by interstitial flow. Isoforms of VEGF such as VEGF121, VEGF165, and VEGF189 displayed different angiogenic properties on the chip as assessed by sprout length and number, vessel perfusion, and connectivity. VEGF165 had the highest capacity to induce vascular sprouting among the three isoforms assessed and furthermore, also induced functional vessel formation. This chip could be used to analyze the effect of different angiogenic factors and drugs, as well as to explore the mechanism of angiogenesis induced by such factors.
Highlights
We found that polarized vascular sprouts were induced by both rVEGF121 and rVEGF165
Our findings suggest that rVEGF165 could induce Primary human umbilical vein endothelial cells (pHUVEC) to generate functional vessels in the presence of upstream Interstitial flow (IF)
We utilized a microfluidic chip for the induction of angiogenesis, and this platform enabled the analysis of angiogenesis stimulated by both angiogenic factors and IF
Summary
Angiogenesis refers to the process of vessel sprouting and growth from pre-existing blood vessels induced by a series of angiogenic factors [1,2]. Stimulated by proangiogenic signals, endothelial cells differentiate into motile and invasive tip cells that grow protruding filopodia. Tip cells are located at the front of new sprouts and guide their direction of growth. Stalk cells proliferate to support the elongation of sprouting and can establish a lumen. Tip cells from neighboring sprouts fuse with each other to build vessel loops (anastomosis), and within the lumen extension and blood flow initiation, the newly formed vessels become perfused [2,3,4,5]. Connectivity and perfusion are important indices with which to evaluate the function of blood vessels
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