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An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases.
Robert, Jerome; Weilinger, Nicholas L; Cao, Li-Ping; Cataldi, Stefano; Button, Emily B; Stukas, Sophie; Martin, Emma M; Seibler, Philip; Gilmour, Megan; Caffrey, Tara M; Rowe, Elyn M; Fan, Jianjia; MacVicar, Brian; Farrer, Matthew J; Wellington, Cheryl L.
Afiliación
  • Robert J; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada. jerome.robert@usz.ch.
  • Weilinger NL; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada. jerome.robert@usz.ch.
  • Cao LP; Institute of Clinical Chemistry, University hospital Zurich, 8000 Zurich, Wagistrasse 14, CH-8952, Schlieren, Switzerland. jerome.robert@usz.ch.
  • Cataldi S; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Button EB; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Stukas S; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Martin EM; Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Seibler P; Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Gilmour M; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Caffrey TM; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Rowe EM; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Fan J; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
  • MacVicar B; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Farrer MJ; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
  • Wellington CL; Institute of Neurogenetics, University of Luebeck, 23562, Luebeck, Germany.
Mol Neurodegener ; 15(1): 70, 2020 11 19.
Article en En | MEDLINE | ID: mdl-33213497
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arterias / Astrocitos / Enfermedades Neurodegenerativas / Células Endoteliales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Neurodegener Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arterias / Astrocitos / Enfermedades Neurodegenerativas / Células Endoteliales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Mol Neurodegener Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido