Engineered 3D vascular and neuronal networks in a microfluidic platform
Name
s41598-018-23512-1.pdf
Size
6.48 MB
Format
Adobe PDF
Checksum (MD5)
d8c148c6408482a3f5cf446e6c10d027
Author(s)
Osaki, Tatsuya
Sivathanu, Vivek
Kamm, Roger Dale
Date Issued
March 2018
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Osaki, Tatsuya et al. “Engineered 3D Vascular and Neuronal Networks in a Microfluidic Platform.” Scientific Reports 8, 1 (March 2018): 5168 © 2018 The Author(s)
Version
Final published version
Abstract
Neurovascular coupling plays a key role in the pathogenesis of neurodegenerative disorders including motor neuron disease (MND). In vitro models provide an opportunity to understand the pathogenesis of MND, and offer the potential for drug screening. Here, we describe a new 3D microvascular and neuronal network model in a microfluidic platform to investigate interactions between these two systems. Both 3D networks were established by co-culturing human embryonic stem (ES)-derived MN spheroids and endothelial cells (ECs) in microfluidic devices. Co-culture with ECs improves neurite elongation and neuronal connectivity as measured by Ca 2+ oscillation. This improvement was regulated not only by paracrine signals such as brain-derived neurotrophic factor secreted by ECs but also through direct cell-cell interactions via the delta-notch pathway, promoting neuron differentiation and neuroprotection. Bi-directional signaling was observed in that the neural networks also affected vascular network formation under perfusion culture. This in vitro model could enable investigations of neuro-vascular coupling, essential to understanding the pathogenesis of neurodegenerative diseases including MNDs such as amyotrophic lateral sclerosis.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Attribution 4.0 International (CC BY 4.0)
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41598-018-23512-1
