CAAT study: lab-grown mini-brains are a good alternative to traditional animal testing


CAAT study: lab-grown mini-brains are a good alternative to traditional animal testing

24 February 2020
Researchers at Johns Hopkins Bloomberg School of Public Health have demonstrated the use of stem-cell-derived "mini-brains" to detect harmful side effects of a common drug on the developing brain.

Mini-brains are miniature human brain models, developed with human cells and barely visible to the human eye, whose cellular mechanisms mimic those of the developing human brain.

The scientists, who will publish their findings on February 21 in Frontiers in Cellular Neuroscience, used the mini-brains to determine that the common antidepressant paroxetine suppresses the growth of synapses, or connection points between neurons, and leads to significant decreases in an important support-cell population. Paroxetine is sold under the brand names Paxil and Seroxat, among others.

Paroxetine, which can cross the placenta in pregnant women, currently comes with a warning against use in early pregnancy, largely due to a known risk of heart and lung defects. Some epidemiological studies also have suggested that paroxetine raises the risk of autism. The new findings are likely to heighten concerns about the effects of this drug, and others in its class, on the developing brain.

The study authors say that the findings suggest that lab-grown mini-brains, which they call BrainSpheres, are a good alternative to traditional animal testing. In particular, they can reveal drugs and other chemicals that are harmful to young brains.

"There's a growing concern that we have an epidemic of neurodevelopmental disorders, including autism, and that these might be caused by exposures to common drugs or other chemicals. However, since traditional animal testing is so expensive, we haven't been able to properly investigate this question," says co-senior author Thomas Hartung, MD, the Doerenkamp-Zbinden Chair and Professor in the Department of Environmental Health and Engineering and director of the Center for Alternatives to Animal Testing at the Bloomberg School.

Hartung and colleagues developed the mini-brains to model early brain development. The tiny clumps of brain tissue are made by taking cells from adult humans, often from their skin, and transforming them into stem cells, and then biochemically nudging the stem cells to develop into young brain cells. The mini-brains form a rudimentary brain-like organization over a period of a few months. Because they are made of human cells, they may be more likely to predict effects on the human brain—and because they can be mass-produced in the lab, they are much cheaper to work with than animals.