Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2024-09-28 DOI:10.1016/j.biomaterials.2024.122864

Georgios Pavlou , Sarah Spitz , Francesca Michela Pramotton , Alice Tsai , Brent M. Li , Xun Wang , Olivia M. Barr , Eunkyung Clare Ko , Shun Zhang , Savannah J. Ashley , Anna Maaser-Hecker , Se Hoon Choi , Mehdi Jorfi , Rudolph E. Tanzi , Roger D. Kamm

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引用次数: 0

Abstract

The blood–brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease. This study introduces a three-dimensional (3D) self-assembled in vitro model of the human neurovascular unit to recapitulate some of the complex interactions between the BBB and AD pathologies. It incorporates primary human brain endothelial cells, pericytes and astrocytes, and stem cell-derived neurons and astrocytes harboring Familial AD (FAD) mutations. Over an extended co-culture period, the model demonstrates increased BBB permeability, dysregulation of key endothelial and pericyte markers, and morphological alterations mirroring AD pathologies. The model enables visualization of amyloid-beta (Aβ) accumulation in both neuronal and vascular compartments. This model may serve as a versatile tool for neuroscience research and drug development to provide insights into the dynamic relationship between vascular dysfunction and AD pathogenesis.

查看原文本刊更多论文

设计阿尔茨海默病三维人体神经血管模型，研究血管功能障碍。

血脑屏障（BBB）是一种选择性过滤器，可防止有害物质进入健康的大脑。血脑屏障功能障碍与多种神经系统疾病有关。在阿尔茨海默病（AD）中，BBB 的破坏在疾病的发生和发展中起着重要作用。本研究引入了一种三维（3D）自组装体外人类神经血管单元模型，以再现 BBB 与阿尔茨海默病病理之间的一些复杂相互作用。它结合了原代人脑内皮细胞、周细胞和星形胶质细胞以及干细胞衍生的神经元和星形胶质细胞，这些细胞都携带家族性AD（FAD）突变。在长时间的共培养过程中，该模型显示出BBB通透性增加、关键内皮细胞和周细胞标志物失调以及反映AD病理的形态学改变。该模型可观察到淀粉样蛋白-β（Aβ）在神经元和血管中的积累。该模型可作为神经科学研究和药物开发的多功能工具，帮助人们深入了解血管功能障碍与AD发病机制之间的动态关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.