Home Health Implementation of a human brain-like tissue on a ‘small chip’… Treatment avenues open for meningitis, etc.

Implementation of a human brain-like tissue on a ‘small chip’… Treatment avenues open for meningitis, etc.

by news dir
■ Yonsei University research team develops artificial chip that mimics ‘blood-brain barrier’

‘Blood-brain barrier’ acts as a brain protector
It also blocks the treatment and halves the effect

Imitated brain tissue on a chip and cultured it
Observation of movement of various substances
Successful modeling of fungal infection

The brain is called the microcosm of the body. This is because it has an independent structure and function that distinguishes it from other organs such as the heart, liver, and lungs. In particular, the brain, which is the commander of the body and mind, is surrounded by a triple barrier.

The last of these is the blood-brain barrier (BBB). It is the innermost defense network of the brain that blocks the intrusion of toxins, drugs, and pathogens from the outside and allows only essential substances to penetrate. The blood-brain barrier is a selective permeable membrane surrounding the central nervous system, such as the brain, and functions to block the passage of pathogens and harmful chemicals that can be infected through the blood. If the outermost barrier, the skull, and the next barrier, the meninges and cerebrospinal fluid (CSF), safely protect the brain from external physical shocks, the blood-brain barrier is a molecular chemical defense network that filters bacteria and chemicals.

The blood-brain barrier is one of the most important brain protectors, but it is also an impregnable castle for doctors who need to administer drugs to treat a sick brain. If the molecules of chemical drugs are blocked by the blood-brain barrier and do not reach the brain, it is difficult to achieve the expected therapeutic effect. Therefore, the development of drugs that can easily cross the blood-brain barrier has emerged as a big task in the scientific community. However, a domestic research team has created for the first time a biochip that can be modeled in a laboratory in advance to see what pathogens or compounds can pass through this barrier, and if so, what it will look like.

The National Research Foundation of Korea recently announced that a research team led by Professor Seung-Woo Cho and Yong-Sun Ban of the Department of Biotechnology at Yonsei University has designed an ‘artificial blood-brain barrier chip’ that mimics the structure and functional characteristics of the blood-brain barrier. Unlike simple cell culture, an organ-on-a-chip made using a semiconductor process can reproduce the microenvironment of the organ to create an environment almost similar to that of a living body.

The research team simulated and cultured brain blood vessels and brain cells on a chip composed of hundreds of micrometers of microchannels, and realized a blood-brain barrier between them. It can be observed under a microscope in real time whether various substances injected with the culture medium through a microchannel that mimics brain blood vessels pass through a selective permeable membrane that mimics the blood-brain barrier and move to an empty room that mimics brain cells.

The core of the technology is a three-dimensional hydrogel that simulates a microenvironment in which cells can grow and controls the flow of the culture medium while culturing neural stem cells, cerebrovascular endothelial cells, and cerebrovascular epithelial cells together. It simulates growth and angiogenesis processes. By implementing human brain tissue containing cerebral blood vessels on a small chip, it is now possible to reproduce the specific function of the blood-brain barrier. It is expected that artificial chips will be widely applied in the development of drug delivery systems that can pass through the blood-brain barrier and reach the brain.

The research team verified that various substances with different molecular weights can act as a selective permeable membrane like a real blood-brain barrier by passing through the permeable membrane of the biochip only when cytokines are treated. Cytokine refers to the body’s defense system signaling substances secreted by immune cells.

In addition, it succeeded in modeling the process of fungal brain infection in this process. The fungus, the cause of meningitis, freely crosses the blood-brain barrier, penetrates into and destroys brain nerve cells, killing 180,000 patients worldwide every year. The research team observed in real time the phenomenon that when pathogenic fungi were injected into the biochip, they moved to the permeable membrane as if they were searching for brain cells and then passed in an aggregated form, and also found genes involved in this. In the meantime, brain infections caused by fungi have been known, but because there are no suitable experimental models, it is not known how the fungus reaches the brain.

This time, it was confirmed that the fungus in which the gene found by the research team was removed does not pass through the blood-brain barrier replica. It is expected to be applied to the discovery of candidate substances that can act on fungal meningitis or the discovery of compounds that can cross the blood-brain barrier. The results of this research, conducted with support from the Ministry of Science and ICT’s basic research support project and brain science source technology development project, were published in the latest issue of Nature Biomedical Engineering, an international scientific journal in the field of biomedical engineering.

Reporter Noh Seong-yeol [email protected]

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