Study will test effects of more than 200 chemicals on ‘organoid’ hearts

Image: Academic Affairs Communications, Research Communications and Public Relations

Though the World Health Organization estimates that up to 23 percent of the global burden of cardiovascular diseases—the leading cause of death worldwide—can be attributed to environmental chemicals, we really don’t know much about these substances.

David Threadgill, Distinguished Professor in the Department of Molecular and Cellular Medicine at the Texas A&M Health Science Center, had been thinking about the problem and possible ways to approach the research.

So when the U.S. Environmental Protection Agency put out a call for proposals to study toxicity using “organoids,” three-dimensional organ–like structures grown in cell culture, he and his collaborators jumped at the opportunity. An organoid has multiple types of cells, just like a real organ does, but it lives entirely within a dish and it is far easier to use for chemical testing. They are thought of as a kind of bridge between conventional, single-layer cell cultures and whole-animal systems.

Together with his long-term collaborator, Ivan Rusyn, professor of veterinary integrative biosciences at the Texas A&M College of Veterinary Medicine & Biomedical Sciences, Threadgill received a $6 million grant from the agency to fund a multi-institutional collaboration to study how heart cells react to different chemicals.

Threadgill’s lab will use induced pluripotent stem (iPS) cells to create little beating organoid “hearts” in culture, with iPS cells coming from 100 different strains of the animal model—creating variation similar to what you would see in the human population.

“We’re looking at population-level exposure,” Threadgill said. “Does everyone respond the same way, or are some people more sensitive?”

Threadgill will then test what happens to the rhythm of the organoids’ “heartbeat” after they are exposed to the nearly 200 environmental chemicals.

“What we hope to be able to show—which has never been formally proven—is that all of this effort to use cultured cells or very simple systems to screen for toxicity is informative for what happens in the whole animal, with its very complex systems,” Threadgill said. “If it is indeed the case that it is predictive, we will have much greater confidence in the results coming out of cell-based research.”