UW-Madison team developing tissue chip to screen neurological toxins

Sept. 23, 2014

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.

Inside wells about a fifth the size of a dime, the team grew neural tissues from a combination of cell types that represent the main components of a developing brain. This image shows the entire structure formed in the well, with nuclei in blue, neurons in green and glial cells in red.

Confocal microscopy image: Michael Schwartz

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 NIH's 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.

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UW-Madison team developing tissue chip to screen neurological toxins