The anti-narcotics slogan “this is your brain on drugs” became famous for its egg-based metaphors about the neurological impacts of substance abuse. But you know what tops the fried egg model? Dosing a sophisticated artificial brain on a polymer chip with methamphetamine, which is exactly what a team of scientists describe in a literally mind-boggling study published on Monday in Nature Biotechnology.
The research was co-led by Ben Maoz, Anna Herland, and Edward Fitzgerald at Harvard’s Wyss Institute for Biologically Inspired Engineering, and represents the latest development in Organ Chip technology. This method of simulating organ functions involves integrating human cell cultures into microfluidic chip platforms, and observing responses to new molecules and stimuli.
In this case, that stimulus was meth. “Our primary reason for choosing this drug is that it is one of the most addictive drugs responsible for thousands of deaths,” Maoz told me in a email. “Given this tragic statistic, it is surprising that much is still unknown. Therefore, we sought to use this novel system to unveil the metabolic effect of meth on the different parts of the [neurovascular unit].”
In other words, these Organ Chip models allow scientists to observe “your brain on drugs,” or at least, a working replica of it. This is promising not only for untangling the effects of commonly abused substances, which could inform better addiction treatments, but for pioneering new ways to deliver helpful drugs to the right targets in the brain.
The Wyss team sought to replicate processes that occur in the blood-brain barrier (BBB). This semipermeable filter acts like a cerebral nightclub bouncer, allowing helpful substances like water and glucose to flow from the bloodstream to the neurons, while denying access to potentially damaging molecules.
To simulate this interplay artificially, the scientists linked a brain chip filled with neural cells to two BBB chips that contained endothelial, astrocyte, and pericyte cells (these are the cell types that govern the BBB). Artificial blood and spinal fluid flowed through the system, enabling molecules to be introduced to the influx BBB chip, which filtered into the brain chip, which in turn fed the efflux BBB chip.
That’s where the meth came in. One of the biggest impacts of methamphetamine is increasing the permeability of the BBB—or, making the bouncer far more tolerant about who gets into the club. When 1.5 millimolars of meth was introduced into the influx BBB chip, about 10% of the dose crossed the barrier, entered the brain chip, and bound to the neurons, mimicking the real neurological effects of the drug.
In addition to drug experiments, chip platforms are applicable to neuropathology research. Cells from patients of stroke, Alzheimer’s disease, traumatic brain injury, or other conditions could be integrated into the chips, or the disease state could be artificially induced with gene-editing methods.
To that point, Maoz, Herland, and Fitzgerald are developing new Organ Chip platforms in their own laboratories at Tel Aviv University, KTH Royal Institute of Technology, and Uppsala University, respectively.
“Currently we have number of studies which involve our system and concept both at the Wyss Institute and in our independent labs,” Maoz said. “One is to build a micro-human on a chip, which will include more organs, and [...] we are aiming to create a single organs on a chip system that will come from one individual.”
In other words, enabling personalized medicine by creating a “mini-me-on-a-chip.”
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