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Microfluidic organ-on-chip technology for blood-brain barrier research.

van der Helm MW, van der Meer AD, Eijkel JC, van den Berg A, Segerink LI - Tissue Barriers (2016)

Bottom Line: Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors.This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models.We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.

View Article: PubMed Central - PubMed

Affiliation: BIOS Lab on a Chip group, MIRA Institute for Biomedical Technology and Technical Medicine & MESA+ Institute for Nanotechnology, University of Twente ; Enschede, The Netherlands.

ABSTRACT
Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and the challenges that are still ahead. The BBB is formed by specialized e3ndothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function. Studying BBB function and dysfunction is important for drug development and biomedical research. Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors. Examples of BBBs-on-chips in literature already show the potential of more realistic microenvironments and the study of organ-level functions. A key challenge in the field of BBB-on-chip development is the current lack of standardized quantification of parameters such as barrier permeability and shear stress. This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models. We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.

No MeSH data available.


Anatomy of the neurovascular unit. A brain capillary comprised of specialized brain endothelial cells forms the blood-brain barrier (BBB). This capillary is surrounded by basal lamina (basement membrane), pericytes and astrocytic end-feet. Also microglia and neurons are in close contact with the BBB. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience, ref. 4, copyright 2006.
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f0001: Anatomy of the neurovascular unit. A brain capillary comprised of specialized brain endothelial cells forms the blood-brain barrier (BBB). This capillary is surrounded by basal lamina (basement membrane), pericytes and astrocytic end-feet. Also microglia and neurons are in close contact with the BBB. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience, ref. 4, copyright 2006.

Mentions: The BBB is part of a larger structure: the neurovascular unit (NVU), consisting of endothelial cells forming the capillary, pericytes, glial cells and neuronal cells, as well as their associated extracellular matrix proteins.1 The NVU anatomy is shown in Figure 1. The brain capillaries are comprised of tightly linked endothelial cells surrounded by pericytes and a basement membrane (30 to 40 nm thick lamina of a.o. collagen IV, laminin and fibronectin).2 The microvessel is also surrounded by astrocytic end-feet and in close contact with microglia and neurons. All these elements have important roles in the formation, maturation and maintenance of the BBB.2,4Figure 1.


Microfluidic organ-on-chip technology for blood-brain barrier research.

van der Helm MW, van der Meer AD, Eijkel JC, van den Berg A, Segerink LI - Tissue Barriers (2016)

Anatomy of the neurovascular unit. A brain capillary comprised of specialized brain endothelial cells forms the blood-brain barrier (BBB). This capillary is surrounded by basal lamina (basement membrane), pericytes and astrocytic end-feet. Also microglia and neurons are in close contact with the BBB. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience, ref. 4, copyright 2006.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836466&req=5

f0001: Anatomy of the neurovascular unit. A brain capillary comprised of specialized brain endothelial cells forms the blood-brain barrier (BBB). This capillary is surrounded by basal lamina (basement membrane), pericytes and astrocytic end-feet. Also microglia and neurons are in close contact with the BBB. Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience, ref. 4, copyright 2006.
Mentions: The BBB is part of a larger structure: the neurovascular unit (NVU), consisting of endothelial cells forming the capillary, pericytes, glial cells and neuronal cells, as well as their associated extracellular matrix proteins.1 The NVU anatomy is shown in Figure 1. The brain capillaries are comprised of tightly linked endothelial cells surrounded by pericytes and a basement membrane (30 to 40 nm thick lamina of a.o. collagen IV, laminin and fibronectin).2 The microvessel is also surrounded by astrocytic end-feet and in close contact with microglia and neurons. All these elements have important roles in the formation, maturation and maintenance of the BBB.2,4Figure 1.

Bottom Line: Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors.This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models.We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.

View Article: PubMed Central - PubMed

Affiliation: BIOS Lab on a Chip group, MIRA Institute for Biomedical Technology and Technical Medicine & MESA+ Institute for Nanotechnology, University of Twente ; Enschede, The Netherlands.

ABSTRACT
Organs-on-chips are a new class of microengineered laboratory models that combine several of the advantages of current in vivo and in vitro models. In this review, we summarize the advances that have been made in the development of organ-on-chip models of the blood-brain barrier (BBBs-on-chips) and the challenges that are still ahead. The BBB is formed by specialized e3ndothelial cells and separates blood from brain tissue. It protects the brain from harmful compounds from the blood and provides homeostasis for optimal neuronal function. Studying BBB function and dysfunction is important for drug development and biomedical research. Microfluidic BBBs-on-chips enable real-time study of (human) cells in an engineered physiological microenvironment, for example incorporating small geometries and fluid flow as well as sensors. Examples of BBBs-on-chips in literature already show the potential of more realistic microenvironments and the study of organ-level functions. A key challenge in the field of BBB-on-chip development is the current lack of standardized quantification of parameters such as barrier permeability and shear stress. This limits the potential for direct comparison of the performance of different BBB-on-chip models to each other and existing models. We give recommendations for further standardization in model characterization and conclude that the rapidly emerging field of BBB-on-chip models holds great promise for further studies in BBB biology and drug development.

No MeSH data available.