An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases
Abstract Introduction The neurovascular unit (NVU) – the interaction between the neurons and the cerebrovasculature – is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is cu...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://link.springer.com/article/10.1186/s13024-020-00418-z |
| _version_ | 1819294504807563264 |
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| author | Jerome Robert Nicholas L. Weilinger Li-Ping Cao Stefano Cataldi Emily B. Button Sophie Stukas Emma M. Martin Philip Seibler Megan Gilmour Tara M. Caffrey Elyn M. Rowe Jianjia Fan Brian MacVicar Matthew J. Farrer Cheryl L. Wellington |
| author_facet | Jerome Robert Nicholas L. Weilinger Li-Ping Cao Stefano Cataldi Emily B. Button Sophie Stukas Emma M. Martin Philip Seibler Megan Gilmour Tara M. Caffrey Elyn M. Rowe Jianjia Fan Brian MacVicar Matthew J. Farrer Cheryl L. Wellington |
| author_sort | Jerome Robert |
| collection | DOAJ |
| description | Abstract Introduction The neurovascular unit (NVU) – the interaction between the neurons and the cerebrovasculature – is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU. Method We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries. Results This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer’s disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model. Conclusion This model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses. |
| first_indexed | 2024-12-24T04:27:23Z |
| format | Article |
| id | doaj.art-bf6b04e51e7642eaa8ed05bcd04de018 |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-24T04:27:23Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-bf6b04e51e7642eaa8ed05bcd04de0182022-12-21T17:15:32ZengBMCMolecular Neurodegeneration1750-13262020-11-0115111810.1186/s13024-020-00418-zAn in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseasesJerome Robert0Nicholas L. Weilinger1Li-Ping Cao2Stefano Cataldi3Emily B. Button4Sophie Stukas5Emma M. Martin6Philip Seibler7Megan Gilmour8Tara M. Caffrey9Elyn M. Rowe10Jianjia Fan11Brian MacVicar12Matthew J. Farrer13Cheryl L. Wellington14Department of Pathology and Laboratory Medicine, University of British ColumbiaDjavad Mowafaghian Centre for Brain Health, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaCentre for Applied Neurogenetics, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaInstitute of Neurogenetics, University of LuebeckDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDjavad Mowafaghian Centre for Brain Health, University of British ColumbiaCentre for Applied Neurogenetics, University of British ColumbiaDepartment of Pathology and Laboratory Medicine, University of British ColumbiaAbstract Introduction The neurovascular unit (NVU) – the interaction between the neurons and the cerebrovasculature – is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently no in vitro 3-dimensional (3D) perfusible model of the human cortical arterial NVU. Method We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries. Results This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It reproduces key characteristics of cortical neurons and astrocytes and enables formation of a selective and functional endothelial barrier. We provide proof-of-principle data showing that this in vitro human arterial NVU may be suitable to study neurovascular components of neurodegenerative diseases such as Alzheimer’s disease (AD), as endogenously produced phosphorylated tau and beta-amyloid accumulate in the model over time. Finally, neuronal and glial fluid biomarkers relevant to neurodegenerative diseases are measurable in our arterial NVU model. Conclusion This model is a suitable research tool to investigate arterial NVU functions in healthy and disease states. Further, the design of the platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.http://link.springer.com/article/10.1186/s13024-020-00418-z |
| spellingShingle | Jerome Robert Nicholas L. Weilinger Li-Ping Cao Stefano Cataldi Emily B. Button Sophie Stukas Emma M. Martin Philip Seibler Megan Gilmour Tara M. Caffrey Elyn M. Rowe Jianjia Fan Brian MacVicar Matthew J. Farrer Cheryl L. Wellington An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases Molecular Neurodegeneration |
| title | An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases |
| title_full | An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases |
| title_fullStr | An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases |
| title_full_unstemmed | An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases |
| title_short | An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases |
| title_sort | in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases |
| url | http://link.springer.com/article/10.1186/s13024-020-00418-z |
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