Giving stem cells the right physical cues produced micro hearts, maybe a tool to avoid birth defects

Heart defects, one of the leading types of birth defects, often result from drugs mom is taking, but we have not had a good model of developing fetal hearts to test drugs for these side effects. Now, a team at the University of California, Berkeley and the Gladstone Institutes has created micro heart chambers in a lab dish by providing the starting stem cells with the right physical cues. And they found these mini-hearts can predict birth defects.

Different types of cells required to make functioning heart tissue show up as different colors here.

Different types of cells required to make functioning heart tissue show up as different colors here.

As we have written before, it takes a neighborhood to raise a stem cell into a wanted adult cell. While most lab cultures maturing stem cells into adult tissue are flat, the developing fetal heart grows in an environment with many physical cues, both chemical and pressure. The Berkeley team added a chemical layer to the cell culture dish and etched it to provide added physical cues. The result produced both connective tissue and heart muscle that were organized into micro heart chambers that could beat.

“We believe it is the first example illustrating the process of a developing human heart chamber in vitro,” said Kevin Healy, co-senior author of the study at UC Berkeley. “This technology could help us quickly screen for drugs likely to generate cardiac birth defects, and guide decisions about which drugs are dangerous during pregnancy.”

The team took the added step of testing a drug known to cause birth defects, thalidomide. When the stem cells were growing with the drug added to the culture, they did not develop into the same micro chambers.

The Berkeley bioengineers started with stem cells reprogrammed from adult skin tissue in the CIRM-funded lab of Bruce Conklin at the Gladstone, the other co-senior author on the paper. These iPS-type stem cells were essential to the project.

“The fact that we used patient-derived human pluripotent stem cells in our work represents a sea change in the field,” said Healy. “Previous studies of cardiac micro-tissues primarily used harvested rat cardiomyocytes, which is an imperfect model for human disease.”

 

Berkeley issued a press release on the work and Popular Science wrote a piece on it complete with a fun embedded video of the beating tissue. The journal Nature Communication ran the original research publication today.

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