Pericytes Contribute Basement Membrane Proteins in a Human Stem Cell-Derived Blood-Brain Barrier Model (Louis Widom’s 2024 MPS World Summit Poster)
20240605_LPW_MPS_Poster_Final
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Assessing the Permeability of Two Barriers in the Post-capillary Neurovascular Unit Part 2: Measuring R2
In Part 1 we explained that the composite barrier in our model of the post-capillary NVU is determined by RBBB = RBlB + R2 + RBrB where is R2 is the resistance of the ‘perivascular space’ in our chip. Unlike the other two, the perivascular space is not a regulated cellular barrier that we need…
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hToC | Knowledge (Public) | memBrains | NRG | μSiM
The Journey to a Manufactured Flow Insert + Protocol for Use
Introduction The modular μSiM is based on a 96-well plate format with a 100 μl open well. While these devices have proven extremely useful for various barrier models including the blood-brain barrier1 and the tendon-vascular interface2, there is a need to transform the open well into a fluidic channel. A closed channel device would enable…
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Effect of Tau on BMEC Monocultures in μSiMs (Rotation Project – Emily Reitz)
Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by accumulation of amyloid beta (Aβ) peptides and neurofibrillary tangles (NFTs) made of aggregates of the protein tau (1,2). It results in the destruction of neurons and their connections due to this accumulation of amyloid beta and tau (3). Tau is a microtubule associated…
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Bacterial Inflammatory Stimulation of the μSiM-BBB Model
Introduction Sepsis refers to an uncontrolled systemic inflammatory response which can result from bacterial blood infections. We have long been interested in developing a sepsis model using the μSiM-BBB platform because the neuroinflammation stemming from sepsis can cause severe BBB disruption. For the majority of our stimulation experiments we have relied on cytomix, a cocktail…
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Assessing the Permeability of Two Barriers in the Post-capillary Neurovascular Unit Part 1: The Problem Statement
The two barrier anatomy of the post-capillary NVU and why it matters At the post-capilliary venule, the blood-brain barrier (BBB) is actually two barriers in series: 1) one created by the pericyte/BMEC layer at the blood interface and 2) one created by astrocytes and the astrocyte-produced glia limitans at the interface with the brain. We’ll…
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Fc Receptor Binding Inhibitor Aggregation Issues in the CAD-LB Platform
Introduction We are interested in exploring whether certain types of extracellular vesicles (EVs) may be more likely to become trapped while crossing the blood-brain barrier (BBB). Specifically, we are curious if EVs possessing certain types of surface integrins might bind to the vascular basement membrane that surrounds the exterior of brain blood vessels to become…
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Development of Arising Retinal Pigment Epithelium-19 (ARPE-19) Barrier Tissues on NPN
Author: Kevin Ling Dysfunction of the outer retinal blood barrier (oRBB), which is composed of the retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris (CC), is implicated in age-related macular degeneration (AMD), which causes irreversible central vision loss [1-4]. AMD is the leading cause of blindness in industrialized countries; it is estimated that by 2040,…
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Modification of Ultrathin Microporous Silicon Nitride Membrane Stiffness for Tissue Barrier Modeling
Introduction: Developing innovative therapeutics and treatment approaches with improved effectiveness and safety necessitates the use of cell co-culture models and barrier environments that mimic in vivo conditions. These models involve culturing two or more cell types together in vitro, allowing researchers to study cellular interactions, signaling pathways, and responses that closely resemble those seen in…
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Using Dual-Scale Membranes as a Model for a ‘Leaky’ BBB
Introduction Many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are associated with an early breakdown of the blood brain barrier (BBB). This includes an increase in permeability and pericyte degradation [1]. We hypothesize that using dual-scale (nanoporous and microporous) membranes in the µSiM-BBB model will create an inherently ‘leaky’ BBB which can be used…
