UW-Madison Team Developing 'Tissue Chip' to Screen Neurological Toxins

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Newswise MADISON, Wis. A multidisciplinary team at the University of Wisconsin-Madison and the Morgridge Institute for Research is creating a faster, more affordable way to screen for neural toxins, helping flag chemicals that may harm human development.

The National Institutes of Health (NIH) announced today that the UW-Madison and Morgridge team is among 11 universities receiving support to continue the promising work as part of the Tissue Chip for Drug Screening program. The team will receive approximately $7 million over the three-year project.

The next phase of the NIH program aims to improve ways of predicting drug safety and effectiveness. Researchers will collaborate to refine existing 3-D human tissue chips and combine them into an integrated system that can mimic the complex functions of the human body.

"We aim to get more treatments to more patients more efficiently," says Christopher P. Austin, director of the NIHs National Center for Advancing Translational Sciences (NCATS). "That is exactly why we are supporting the development of human tissue chip technology, which could be revolutionary in providing a faster, more cost-effective way of predicting the failure or success of drugs prior to investing in human clinical trials."

The UW-Madison team has succeeded in getting human pluripotent stem cell-derived neural progenitor cells to grow in a 3-D hydrogel environment. From there, the cells differentiate, self-organize, and mature into complex neural tissues. About one-fifth the circumference of a dime, the microenvironments assemble into three-dimensional tissue models that mimic the structure and function of the developing brain.

In tandem with the biological work, the team is testing a machine-learning algorithm that can predict toxic responses to compounds added to these constructed environments. Early results on a 2-D system with 45 known toxins or control compounds produced 100 percent accuracy.

But the human health implications are even broader, says James Thomson, director of regenerative biology for Morgridge Institute and principal investigator on the project. Modern society is awash in chemicals, with millions of existing compounds and thousands of new ones added to regular use every year. Yet surprisingly little is known about the human development impact of these compounds, Thomson says.

There is a tremendous need to come up with high-throughput methods to classify compounds quickly as dangerous or not dangerous, Thomson says. The vast majority of compounds today are not tested at all. We need to proactively identify the bad ones and test those intensively.

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UW-Madison Team Developing 'Tissue Chip' to Screen Neurological Toxins