کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6484322 1416087 2018 39 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes
چکیده انگلیسی
The blood-brain barrier (BBB) regulates molecular trafficking, protects against pathogens, and prevents efficient drug delivery to the brain. Models to date failed to reproduce the human anatomical complexity of brain barriers, contributing to misleading results in clinical trials. To overcome these limitations, a novel 3-dimensional BBB microvascular network model was developed via vasculogenesis to accurately replicate the in vivo neurovascular organization. This microfluidic system includes human induced pluripotent stem cell-derived endothelial cells, brain pericytes, and astrocytes as self-assembled vascular networks in fibrin gel. Gene expression of membrane transporters, tight junction and extracellular matrix proteins, was consistent with computational analysis of geometrical structures and quantitative immunocytochemistry, indicating BBB maturation and microenvironment remodelling. Confocal microscopy validated microvessel-pericyte/astrocyte dynamic contact-interactions. The BBB model exhibited perfusable and selective microvasculature, with permeability lower than conventional in vitro models, and similar to in vivo measurements in rat brain. This robust and physiologically relevant BBB microvascular model offers an innovative and valuable platform for drug discovery to predict neuro-therapeutic transport efficacy in pre-clinical applications as well as recapitulate patient-specific and pathological neurovascular functions in neurodegenerative disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 180, October 2018, Pages 117-129
نویسندگان
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