title: A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier.
abstract: The neurovascular unit is a complex, interdependent system composed of neurons and neural supporting cells, such as astrocytes, as well as cells that comprise the vascular system including endothelial cells, pericytes, and smooth muscle cells. Each cell type in the neurovascular unit plays an essential role, either in transmitting and processing neural signals or in maintaining the appropriate microenvironmental conditions for healthy neural function. In vitro neurovascular models can be useful for understanding the different roles and functions of the cells composing the neurovascular unit, as well as for assessing the effects on neural function of therapeutic compounds after crossing the endothelial barrier. Here, we report a novel three-dimensional neurovascular microfluidic model consisting of primary rat astrocytes and neurons together with human cerebral microvascular endothelial cells. These three cell types in our neurovascular chip (NVC) show distinct cell type-specific morphological characteristics and functional properties. In particular, morphological and functional analysis of neurons enables quantitative assessment of neuronal responses, while human cerebral endothelial cells form monolayers with size-selective permeability similar to existing in vitro blood-brain barrier (BBB) models.
authors.affiliation: Singapore-MIT Alliance for Research and Technology, 138602 Singapore.
authors.forename: Giulia
authors.initials: G
authors.lastname: Adriani
authors.affiliation: Department of Research, National Neuroscience Institute, 20 College Road, 169856 Singapore and Neuroscience Academic Clinical Programme, Duke-NUS Medical School, 169857 Singapore. Eyleen_Goh@nni.com.sg.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ma
authors.affiliation: Singapore-MIT Alliance for Research and Technology, 138602 Singapore.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pavesi
authors.affiliation: Singapore-MIT Alliance for Research and Technology, 138602 Singapore and Massachusetts Institute of Technology, Cambridge, MA, 02139 USA. rdkamm@mit.edu.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kamm
authors.affiliation: Department of Research, National Neuroscience Institute, 20 College Road, 169856 Singapore and Neuroscience Academic Clinical Programme, Duke-NUS Medical School, 169857 Singapore. Eyleen_Goh@nni.com.sg and Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore and KK Research Center, KK Women's and Children's Hospital, Singapore 229899, Singapore.
authors.forename: Eyleen L K
authors.initials: EL
authors.lastname: Goh
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques / Q000295:instrumentation / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D044085:Microfluidics / Q000295:instrumentation; D008954:Models, Biological; D016501:Neurites; D009474:Neurons / Q000166:cytology / Q000378:metabolism