You prepare a table before me in the presence of my enemies; You anoint my head with oil; my cup overflows. Psalms 23:5 (The Israel Bible™)
The brain – the most important, delicate and complex organ in the body – does its utmost to protect itself from outside dangers. Consisting of 100 billion neurons that control all our thoughts and actions, the brain needs special protection against toxins.
The blood vessels that supply the brain with oxygen and nutrients are very selective about the substances that can pass from the blood to the brain and vice versa, so they are called the brain-blood barrier. Beyond being a physical obstacle, the checkpoint actively regulates brain functions. However, until now, it has not been clear how this regulation was actually implemented.
A Tel Aviv University researcher has now built a “human brain on a chip” and shown how the blood vessels “communicate” with our neurons. Claimed as an important “breakthrough,” the researchers say it will enable improved development of medications for neurodegenerative disorders including Parkinson’s and Alzheimer’s disease. The results of the new study were published recently in the journal Nature Biotechnology. It will also reduce the need for experimentation on animals.
Dr. Ben Meir Maoz of the TAU’s biomedical engineering department and Sagol School of Neuroscience, in cooperation with colleagues from Harvard University, the Swedish Medical Nanoscience Center and the Karolinska Institute in Stockholm, created a model that mimics the passage of fluids from the blood to the human brain through an “organ-on-a-chip.”
“We know that there is a connection between the blood vessels of the brain and brain activity itself,” explains Maoz. “It is very difficult to understand the interaction between blood vessels and nerve cells at the cellular level. Naturally, it is impossible to experiment on a living human brain, whereas cells in cultures do not reflect this connectivity. The interconnectivity of the cells greatly influences their properties. Neurons grown in a petri dish are different in their properties from nerve cells that are attached to blood vessels,” he adds.
“More than 60% of the drugs that successfully pass experiments on animals fail in experiments on humans,” he notes. “Despite the similarities, a simple mouse brain is not a human brain. Moreover, neurodegenerative diseases are diseases characteristic of humans.
The solution that Maoz found was an organ-on-chip – the growth of human tissue from donated tissues and stem cells converted into organ cells. As a result, the activity of the organ can be simulated in a controlled manner and connect the different parts of the brain.
“An organ on a chip is a technology invented a decade ago,” explains the Tel Aviv University scientist, “but its application to understanding basic biological processes in the brain was very limited. The reason for this was that until now we had examined brain tissue detached from the blood barrier. Now we have created a complete system and proved that it works. Thus, for example, we introduced methamphetamine to the blood cell chips, and we saw that we were getting the same symptoms as those who use the drug on the brain chip.”
After a series of successful experiments designed to test the system, the team showed for the first time that blood vessels in the brain not only expand and contract but release chemicals that directly affect nerve cells, streamlining and accelerating their activity as an integral part of the neurological process.
“The brain we have built in the laboratory enables us to examine complex biological processes and the effect of drugs on humans without endangering anyone, and without harming animals, in an efficient way. An organ-on-chip is not only a research tool. The US Food and Drug Administration has already initiated the development of organ-on-chips as part of the drug development process, and a number of collaborations have been established between my laboratory and pharmaceutical companies from Israel and abroad,” says Maoz.
“We are adding additional organs, such as an immune system and liver, to finally build a whole human body model on chips that will replace the need for animals in the lab and will give researchers unprecedented resolutions on the effects of various chemicals on the human brain – and the biological development of various diseases unique to humans,” he concludes.