Vascularizing the brain <i>in vitro</i>

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Summary

The brain is arguably the most fascinating and complex organ in the human body. Recreating the brain in vitro is an ambition restricted by our limited understanding of its structure and interacting elements. One of these interacting parts, the brain microvasculature, is distinguished by a highly selective barrier known as the blood-brain barrier (BBB), limiting the transport of substances between the blood and the nervous system. Numerous in vitro models have been used to mimic the BBB and constructed by implementing a variety of microfabrication and microfluidic techniques. However, currently available models still cannot accurately imitate the in vivo characteristics of BBB. In this article, we review recent BBB models by analyzing each parameter affecting the accuracy of these models. Furthermore, we propose an investigation of the synergy between BBB models and neuronal tissue biofabrication, which results in more advanced models, including neurovascular unit microfluidic models and vascularized brain organoid-based models.

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Biotechnology; Tissue Engineering; Materials science; Biomaterials

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Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

Kazutoshi Takahashi, Koji TANABE, Mari Ohnuki … (2007)

Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.

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An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex.

Ye Zhang, Kenian Chen, Steven A Sloan … (2014)

The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain. Copyright © 2014 the authors 0270-6474/14/3411929-19$15.00/0.

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The blood-brain barrier.

Richard Daneman, Alexandre Prat (2015)

Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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Author and article information

Contributors

Liang Ma

Journal

Journal ID (nlm-ta): iScience

Journal ID (iso-abbrev): iScience

Title: iScience

Publisher: Elsevier

ISSN (Electronic): 2589-0042

Publication date PMC-release: 17 March 2022

Publication date Collection: 15 April 2022

Publication date (Electronic): 17 March 2022

Volume: 25

Issue: 4

Electronic Location Identifier: 104110

Affiliations

[1 ]State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310058, China

[2 ]School of Mechanical Engineering, Zhejiang University, Hangzhou 310058, China

[3 ]The Affiliated Stomatologic Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China

[4 ]School of Materials Science and Engineering, Tongji University, Shanghai 201804, China

[5 ]Division of Engineering in Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, USA

Author notes

[∗ ]Corresponding author liangma@ 123456zju.edu.cn

[6]

These authors contributed equally

Article

Publisher Item ID: S2589-0042(22)00380-7 Publisher ID: 104110

DOI: 10.1016/j.isci.2022.104110

PMC ID: 8976127

PubMed ID: 35378862

SO-VID: 1c25af1e-c910-4cec-9f6c-e866135f9fc5

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Vascularizing the brain in vitro

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Science of nonlocal Consciousness

Most cited references 239

Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex.

The blood-brain barrier.

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