Bull, Daniel;
Schweitzer, Christophe;
Bichsel, Colette;
Britschgi, Markus;
Gutbier, Simon;
(2022)
Generation of an hiPSC-Derived Co-Culture System to Assess the Effects of Neuroinflammation on Blood-Brain Barrier Integrity.
Cells
, 11
(3)
, Article 419. 10.3390/cells11030419.
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Abstract
The blood-brain barrier (BBB) regulates the interaction between the highly vulnerable central nervous system (CNS) and the peripheral parts of the body. Disruption of the BBB has been associated with multiple neurological disorders, in which immune pathways in microglia are suggested to play a key role. Currently, many in vitro BBB model systems lack a physiologically relevant microglia component in order to address questions related to the mechanism of BBB integrity or the transport of molecules between the periphery and the CNS. To bridge this gap, we redefined a serum-free medium in order to allow for the successful co-culturing of human inducible pluripotent stem cell (hiPSC)-derived microglia and hiPSC-derived brain microvascular endothelial-like cells (BMECs) without influencing barrier properties as assessed by electrical resistance. We demonstrate that hiPSC-derived microglia exposed to lipopolysaccharide (LPS) weaken the barrier integrity, which is associated with the secretion of several cytokines relevant in neuroinflammation. Consequently, here we provide a simplistic humanised BBB model of neuroinflammation that can be further extended (e.g., by addition of other cell types in a more complex 3D architecture) and applied for mechanistic studies and therapeutic compound profiling.
| Type: | Article |
|---|---|
| Title: | Generation of an hiPSC-Derived Co-Culture System to Assess the Effects of Neuroinflammation on Blood-Brain Barrier Integrity |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/cells11030419 |
| Publisher version: | https://doi.org/10.3390/cells11030419 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, microglia, brain microvascular endothelial cells (BMECs), neuroinflammation, blood-brain barrier (BBB) integrity, transendothelial electrical resistance (TEER), hiPSC co-culture, cytokine secretion, transwell, neurovascular unit (NVU), ALZHEIMERS-DISEASE, NEUROVASCULAR UNIT, PARKINSON DISEASE, MICROGLIA, EXPRESSION, HEALTH, CELLS, BETA, INFILTRATION, METAANALYSIS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10161820 |
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