Engineered 3D vascular and neuronal networks in a microfluidic platform
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 neur...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/115188 https://orcid.org/0000-0002-4177-3515 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1811084661364883456 |
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| author | Osaki, Tatsuya Sivathanu, Vivek Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Osaki, Tatsuya Sivathanu, Vivek Kamm, Roger Dale |
| author_sort | Osaki, Tatsuya |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:54:44Z |
| format | Article |
| id | mit-1721.1/115188 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:54:44Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1151882022-09-28T10:53:21Z Engineered 3D vascular and neuronal networks in a microfluidic platform Osaki, Tatsuya Sivathanu, Vivek Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Osaki, Tatsuya Sivathanu, Vivek Kamm, Roger Dale 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. National Science Foundation (U.S.) (Grant CBET-0939511) 2018-05-02T18:40:57Z 2018-05-02T18:40:57Z 2018-03 2017-11 2018-04-27T16:48:32Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/115188 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) https://orcid.org/0000-0002-4177-3515 https://orcid.org/0000-0002-7232-304X http://dx.doi.org/10.1038/s41598-018-23512-1 Scientific Reports Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Scientific Reports |
| spellingShingle | Osaki, Tatsuya Sivathanu, Vivek Kamm, Roger Dale Engineered 3D vascular and neuronal networks in a microfluidic platform |
| title | Engineered 3D vascular and neuronal networks in a microfluidic platform |
| title_full | Engineered 3D vascular and neuronal networks in a microfluidic platform |
| title_fullStr | Engineered 3D vascular and neuronal networks in a microfluidic platform |
| title_full_unstemmed | Engineered 3D vascular and neuronal networks in a microfluidic platform |
| title_short | Engineered 3D vascular and neuronal networks in a microfluidic platform |
| title_sort | engineered 3d vascular and neuronal networks in a microfluidic platform |
| url | http://hdl.handle.net/1721.1/115188 https://orcid.org/0000-0002-4177-3515 https://orcid.org/0000-0002-7232-304X |
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