Angiogenic responses in a 3D micro-engineered environment of primary endothelial cells and pericytes
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10456_2020_9746_ReferencePDF.pdf
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Author(s)
Bai, Jing
Khajavi, Mehrdad
Sui, Lufei
Fu, Haojie
Tarakkad Krishnaji, Subrahmanian
Birsner, Amy E.
Bazinet, Lauren
Kamm, Roger D.
D’Amato, Robert J.
Date Issued
September 21, 2020
Publisher
Springer Netherlands
Version
Author's final manuscript
Abstract
Abstract
Angiogenesis plays a key role in the pathology of diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. Understanding the driving forces of endothelial cell migration and organization, as well as the time frame of these processes, can elucidate mechanisms of action of important pathological pathways. Herein, we have developed an organ-specific microfluidic platform recapitulating the in vivo angiogenic microenvironment by co-culturing mouse primary brain endothelial cells with brain pericytes in a three-dimensional (3D) collagen scaffold. As a proof of concept, we show that this model can be used for studying the angiogenic process and further comparing the angiogenic properties between two different common inbred mouse strains, C57BL/6J and 129S1/SvlmJ. We further show that the newly discovered angiogenesis-regulating gene Padi2 promotes angiogenesis through Dll4/Notch1 signaling by an on-chip mechanistic study. Analysis of the interplay between primary endothelial cells and pericytes in a 3D microfluidic environment assists in the elucidation of the angiogenic response.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1007/s10456-020-09746-6
