Studying the blood-brain barrier on a microfluidic chip

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Abstract

A realistic model of the blood-brain barrier (BBB) is valuable to perform drug screening experiments and to improve the understanding of the barrier's physiology at normal and pathological conditions. Although the conventional in vitro systems (e.g. Transwell systems) have been used for this, they lack reproducibility and have a static environment. To overcome these disadvantages so called “organs-on-chips‿ have been developed, which use microfluidics and (human) cells to mimic organ function. An example of the BBB chip is shown in the work of Griep et al., where human cerebral endothelial cells (hCMEC/D3) were cultured in a microfluidic device made of polydimethyl siloxane (PDMS). Recently we improved this model. Two PDMS parts with microchannels are placed on top of each other, with a porous membrane in between at the intersection serving as scaffold for the cells. hCMEC/D3 cells (kindly provided by INSERM, Paris, France) were cultured in the chip for up to 15 days. With the four integrated electrodes, which did not block view on the intersection, reliable transendothelial electrical resistance measurements were carried out. Additionally, using immunohistochemistry it was shown that the endothelium expressed tight junction proteins, which is an essential characteristic of the BBB. To further improve the physiological relevance of this promising platform, the cells inside the channels will be cultured under fluid flow. As application, this platform will be used to study the transport of nanocarriers with Alzheimer medication through the BBB. In addition, the clearance of Alzheimer-associated proteins (amyloid β) by the BBB can be examined.
Original languageUndefined
Pages313-314
Number of pages2
DOIs
Publication statusPublished - Dec 2015

Keywords

  • EWI-27570
  • IR-103138
  • METIS-320935

Cite this

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title = "Studying the blood-brain barrier on a microfluidic chip",
abstract = "A realistic model of the blood-brain barrier (BBB) is valuable to perform drug screening experiments and to improve the understanding of the barrier's physiology at normal and pathological conditions. Although the conventional in vitro systems (e.g. Transwell systems) have been used for this, they lack reproducibility and have a static environment. To overcome these disadvantages so called “organs-on-chips‿ have been developed, which use microfluidics and (human) cells to mimic organ function. An example of the BBB chip is shown in the work of Griep et al., where human cerebral endothelial cells (hCMEC/D3) were cultured in a microfluidic device made of polydimethyl siloxane (PDMS). Recently we improved this model. Two PDMS parts with microchannels are placed on top of each other, with a porous membrane in between at the intersection serving as scaffold for the cells. hCMEC/D3 cells (kindly provided by INSERM, Paris, France) were cultured in the chip for up to 15 days. With the four integrated electrodes, which did not block view on the intersection, reliable transendothelial electrical resistance measurements were carried out. Additionally, using immunohistochemistry it was shown that the endothelium expressed tight junction proteins, which is an essential characteristic of the BBB. To further improve the physiological relevance of this promising platform, the cells inside the channels will be cultured under fluid flow. As application, this platform will be used to study the transport of nanocarriers with Alzheimer medication through the BBB. In addition, the clearance of Alzheimer-associated proteins (amyloid β) by the BBB can be examined.",
keywords = "EWI-27570, IR-103138, METIS-320935",
author = "{van der Helm}, {Marieke Willemijn} and Kerensa Broersen and {van der Meer}, {Andries Dirk} and Eijkel, {Jan C.T.} and {van den Berg}, Albert and Segerink, {Loes Irene}",
note = "10.1089/aivt.2015.29000.abstracts",
year = "2015",
month = "12",
doi = "10.1089/aivt.2015.29000.abstracts",
language = "Undefined",
pages = "313--314",

}

Studying the blood-brain barrier on a microfluidic chip. / van der Helm, Marieke Willemijn; Broersen, Kerensa; van der Meer, Andries Dirk; Eijkel, Jan C.T.; van den Berg, Albert; Segerink, Loes Irene.

2015. 313-314.

Research output: Contribution to conferenceAbstractOther research output

TY - CONF

T1 - Studying the blood-brain barrier on a microfluidic chip

AU - van der Helm, Marieke Willemijn

AU - Broersen, Kerensa

AU - van der Meer, Andries Dirk

AU - Eijkel, Jan C.T.

AU - van den Berg, Albert

AU - Segerink, Loes Irene

N1 - 10.1089/aivt.2015.29000.abstracts

PY - 2015/12

Y1 - 2015/12

N2 - A realistic model of the blood-brain barrier (BBB) is valuable to perform drug screening experiments and to improve the understanding of the barrier's physiology at normal and pathological conditions. Although the conventional in vitro systems (e.g. Transwell systems) have been used for this, they lack reproducibility and have a static environment. To overcome these disadvantages so called “organs-on-chips‿ have been developed, which use microfluidics and (human) cells to mimic organ function. An example of the BBB chip is shown in the work of Griep et al., where human cerebral endothelial cells (hCMEC/D3) were cultured in a microfluidic device made of polydimethyl siloxane (PDMS). Recently we improved this model. Two PDMS parts with microchannels are placed on top of each other, with a porous membrane in between at the intersection serving as scaffold for the cells. hCMEC/D3 cells (kindly provided by INSERM, Paris, France) were cultured in the chip for up to 15 days. With the four integrated electrodes, which did not block view on the intersection, reliable transendothelial electrical resistance measurements were carried out. Additionally, using immunohistochemistry it was shown that the endothelium expressed tight junction proteins, which is an essential characteristic of the BBB. To further improve the physiological relevance of this promising platform, the cells inside the channels will be cultured under fluid flow. As application, this platform will be used to study the transport of nanocarriers with Alzheimer medication through the BBB. In addition, the clearance of Alzheimer-associated proteins (amyloid β) by the BBB can be examined.

AB - A realistic model of the blood-brain barrier (BBB) is valuable to perform drug screening experiments and to improve the understanding of the barrier's physiology at normal and pathological conditions. Although the conventional in vitro systems (e.g. Transwell systems) have been used for this, they lack reproducibility and have a static environment. To overcome these disadvantages so called “organs-on-chips‿ have been developed, which use microfluidics and (human) cells to mimic organ function. An example of the BBB chip is shown in the work of Griep et al., where human cerebral endothelial cells (hCMEC/D3) were cultured in a microfluidic device made of polydimethyl siloxane (PDMS). Recently we improved this model. Two PDMS parts with microchannels are placed on top of each other, with a porous membrane in between at the intersection serving as scaffold for the cells. hCMEC/D3 cells (kindly provided by INSERM, Paris, France) were cultured in the chip for up to 15 days. With the four integrated electrodes, which did not block view on the intersection, reliable transendothelial electrical resistance measurements were carried out. Additionally, using immunohistochemistry it was shown that the endothelium expressed tight junction proteins, which is an essential characteristic of the BBB. To further improve the physiological relevance of this promising platform, the cells inside the channels will be cultured under fluid flow. As application, this platform will be used to study the transport of nanocarriers with Alzheimer medication through the BBB. In addition, the clearance of Alzheimer-associated proteins (amyloid β) by the BBB can be examined.

KW - EWI-27570

KW - IR-103138

KW - METIS-320935

U2 - 10.1089/aivt.2015.29000.abstracts

DO - 10.1089/aivt.2015.29000.abstracts

M3 - Abstract

SP - 313

EP - 314

ER -