Document Type
Article
Publication Date
2015
College/Unit
Statler College of Engineering and Mining Resources
Department/Program/Center
Lane Department of Computer Science and Electrical Engineering
Abstract
Microfluidic technologies enable in vitro studies to closely simulate in vivo microvessel environment with complexity. Such method overcomes certain constrains of the statically cultured endothelial monolayers and enables the cells grow under physiological range of shear flow with geometry similar to microvessels in vivo. However, there are still existing knowledge gaps and lack of convincing evidence to demonstrate and quantify key biological features of the microfluidic microvessels. In this paper, using advanced micromanufacturing and microfluidic technologies, we presented an engineered microvessel model that mimicked the dimensions and network structures of in vivo microvessels with a long-term and continuous perfusion capability, as well as high-resolution and real-time imaging capability. Through direct comparisons with studies conducted in intact microvessels, our results demonstrated that the cultured microvessels formed under perfused conditions recapitulated certain key features of the microvessels in vivo. In particular, primary human umbilical vein endothelial cells were successfully cultured the entire inner surfaces of the microchannel network with well-developed junctions indicated by VE-cadherin staining. The morphological and proliferative responses of endothelial cells to shear stresses were quantified under different flow conditions which was simulated with three-dimensional shear dependent numerical flow model. Furthermore, we successfully measured agonist-induced changes in intracellular Ca2+ concentration and nitric oxide production at individual endothelial cell levels using fluorescence imaging. The results were comparable to those derived from individually perfused intact venules. With in vivovalidation of its functionalities, our microfluidic model demonstrates a great potential for biological applications and bridges the gaps between in vitro and in vivo microvascular research.
Digital Commons Citation
Li, Xiang; Xu, Sulei; He, Pingnian; and Liu, Yuxin, "In Vitro Recapitulation of Functional Microvessels for the Study of Endothelial Shear Response, Nitric Oxide and [Ca2+]i" (2015). Faculty & Staff Scholarship. 2240.
https://researchrepository.wvu.edu/faculty_publications/2240
Source Citation
Li X, Xu S, He P, Liu Y (2015) In Vitro Recapitulation of Functional Microvessels for the Study of Endothelial Shear Response, Nitric Oxide and [Ca2+]i. PLoS ONE 10(5): e0126797. https://doi.org/10.1371/journal.pone.0126797
Comments
© 2015 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited