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JoVE Journal
Developmental Biology
生成基于人类 iPSC 的血脑屏障芯片
生成基于人类 iPSC 的血脑屏障芯片
JoVE Journal
Developmental Biology
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JoVE Journal Developmental Biology
Generation of a Human iPSC-Based Blood-Brain Barrier Chip

生成基于人类 iPSC 的血脑屏障芯片

Full Text
13,718 Views
10:20 min
March 2, 2020

DOI: 10.3791/60925-v

Srikanth Jagadeesan1,2,3, Michael J. Workman4, Anna Herland5,6, Clive N. Svendsen4, Gad D. Vatine1,2,3

1The Department of Physiology and Cell Biology, Faculty of Health Sciences,Ben-Gurion University of the Negev, 2The Regenerative Medicine and Stem Cell (RMSC) Research Center,Ben-Gurion University of the Negev, 3The Zlotowski Center for Neuroscience,Ben-Gurion University of the Negev, 4The Board of Governors Regenerative Medicine Institute,Cedars-Sinai Medical Center, 5Division of Micro and Nanosystems,KTH Royal Institute of Technology, 6AIMES, Department of Neuroscience,Karolinska Institutet

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Overview

This protocol demonstrates the generation of a personalized microfluidic blood-brain barrier (BBB) using differentiated induced pluripotent stem cells (iPSCs) on an organ-on-chip platform. This technology allows for the prediction of central nervous system drug permeability and the study of neurological disorders.

Key Study Components

Area of Science

  • Neuroscience
  • Biomedical Engineering
  • Drug Development

Background

  • The blood-brain barrier is crucial for maintaining brain homeostasis.
  • Personalized BBB chips can be derived from iPSCs of individuals with genetic neurological diseases.
  • Understanding the BBB's role in health and disease is essential for advancing neurological research.
  • Pharmaceutical companies can utilize this platform for drug screening.

Purpose of Study

  • To create a fully human, personalized BBB-on-chip.
  • To predict CNS drug permeability.
  • To investigate the role of the BBB in neurological disorders.

Methods Used

  • Seeding differentiated iPSCs on an organ-on-chip.
  • Utilizing microfluidic technology for BBB modeling.
  • Assessing drug penetrability through the BBB.
  • Studying neurological disease mechanisms using personalized chips.

Main Results

  • Successful generation of a personalized BBB chip.
  • Demonstrated ability to predict drug permeability.
  • Provided insights into the BBB's involvement in neurological diseases.
  • Facilitated a platform for pharmaceutical drug screening.

Conclusions

  • The personalized BBB chip is a valuable tool for neuroscience research.
  • This method can enhance understanding of CNS drug delivery.
  • It opens new avenues for studying neurological disorders.

Frequently Asked Questions

What is the blood-brain barrier?
The blood-brain barrier is a selective permeability barrier that protects the brain from harmful substances while allowing necessary nutrients to pass through.
How are iPSCs used in this study?
Induced pluripotent stem cells are differentiated and seeded on an organ-on-chip to create a personalized blood-brain barrier model.
What is the significance of a personalized BBB chip?
A personalized BBB chip allows for the study of individual responses to drugs and the effects of specific neurological diseases on the barrier's function.
Can pharmaceutical companies use this technology?
Yes, pharmaceutical companies can use this platform to screen the penetrability of candidate drugs into the human brain.
What are the potential applications of this research?
This research can be applied to drug development, understanding neurological diseases, and improving CNS drug delivery systems.

血脑屏障(BBB)是一种多细胞神经血管单元,严密调节大脑平衡。通过结合人类 iPSC 和芯片上器官技术,我们生成了个性化的 BBB 芯片,适用于疾病建模和 CNS 药物渗透性预测。介绍了BBB芯片的生成和运行的详细方案。

该协议将展示如何分化诱导多能干细胞在片上器官上播种,以产生一个完全人性化的、个性化的微流体血脑屏障,可用于预测中枢神经系统药物的渗透性,并研究神经系统疾病。使用市售的片上器官,我们将演示任何面向生物的实验室如何使用这项技术来生成个性化的微流体血脑芯片屏障。累积的证据表明,BBB通过产生源自遗传神经系统疾病个体的 iPSC 的个性化 BBB 芯片,在神经系统疾病中发挥作用。

研究BBB在健康和疾病中的作用是可能的。这种方法对制药公司也很有用,它可以使用这个人类BBB平台来筛选候选神经药物进入人脑的可接受性。在片上应用器官技术通常需要专门的工程技能。

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