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    Brain Organ Chips Help Study Effects of Drug and Disease

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    The human brain is one of the most complex mechanisms in the world. After years of research, we only understand a small fraction of the brain. There are quite a few mysteries yet to be unfolded. However, because of the complex nature of the brain, even small discoveries on it have large ripple effects. A recent study conducted by a team of scientists at Harvard University’s Wyss Institute for Biologically Inspired Engineering made a few discoveries of immense interest. Their research focused on the blood-brain barrier(BBB), which is a large network that filters out undesirable molecules that may enter the brain.

    Astrocyte and Pericyte cells collectively known as the neurovascular unit, play an important supporting role in the BBB. They serve as a toxin-filtering last line of defence. The objective of the research was to find different ways in which BBB cells work in the brain. For this, they used novel micro-fluidically linked Organ Chips. They tested the effect of the drug methamphetamine on the neurovascular unit. They wanted to observe the way in which it would disrupt this natural process of brain function.

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    The chips allowed the scientists to not only mimic the effects of certain drugs on the brain (using a BBB chip that has a channel lined with endothelial cells through which flows a culture medium that mimics blood), but also to observe the brain’s functionality in a new way. “Unlike today’s research on Organ Chips which is focused on trying to pack more cell types onto each chip to approximate the complexity of whole organs, we allowed the research team to do the opposite and divide one organ onto multiple chips,” shared first author Ben Maoz, Ph.D., a former Technology Development Fellow at the Wyss Institute.

    The modular nature of the BBB-brain chip system allowed the researchers to individually analyse all the molecules secreted by discrete cell populations. These chips were then connected to trace where they travelled. The chemicals secreted by the cells on the uncoupled BBB chip were largely related to neuron maintenance and protection, demonstrating that the molecules produced by the BBB give neurons chemical cues.

    This study on BBB interaction revealed a clear message: blood vessel health is directly linked to how the brain functions. Kit Parker, Ph.D., a Core Faculty member of the Wyss Institute, was equally enthusiastic in citing the significance of the research study: “The big breakthrough here is that not only have we created a new model for studying the effects of drugs on the human brain, along the way we teased out the communication networks between cells in a way that never could have been done with traditional brain research techniques,” she said, adding, “We are seeing here an unanticipated level of complexity that raises the bar in terms of what it will mean to successfully map the brain’s connectome.”

    Their research was published in journal Nature Biotechnology in an article titled “A linked organ-on-chip model of the human neurovascular unit reveals the metabolic coupling of endothelial and neuronal cells.” The research does seem like a huge breakthrough because it has opened a new world of inferences. It’ll be interesting to see further conjectures and implementations on the subject.

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