It’s an epic feat just to cultivate beating human heart cells on a chip, as researchers at Berkeley did earlier this year. But now, those scientists have gone a step further, mimicking human tissue formation in vitro. For the first time ever, humans have created small heart microchambers replete with pulsating heart cells from genetically reprogrammed stem cells.
Just take a look at this short video showing heart muscle cells in hot pink and fibroblasts (cells that hold the tissue together) in green, holding the heart microchambers to the culture dish.
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“We believe it is the first example illustrating the process of developing a human heart chamber in vitro,” Kevin Healy, co-author of the study and a bioengineer at Berkeley, said in a press statement. “The fact that we used patient-derived human pluripotent stem cells in our work represents a sea change in the field.”
Healy said that previous studies of cardiac microtissues generally used harvested rat cells, which is an “imperfect model for human disease.”
The researchers believe that this technology could help them screen more effectively for drugs which might lead to cardiac birth defects, afford them better insights into drugs that might be dangerous during pregnancy, and potentially eliminate the need for animal testing in the future.
In a paper published in Nature Communications, they describe using stem cells genetically reprogrammed from adult skin tissue and placing these undifferentiated pluripotent stem cells onto a circular-patterned surface—which regulate cell differentiation—to grow.
After two weeks, the cells started to develop into a beating 3D microchamber. The cells also grew differently, depending on where they were located on the surface environment. Cells in the center of the colony developed into cardiac muscle cells, whereas cells along the perimeter developed into fibroblasts—cells that generate collagen and hold tissue together.
“The confined geometric pattern provided biochemical and biophysical cues that directed cardiac differentiation and the formation of a beating microchamber,” Zhen Ma, the study’s lead author, said in a press statement. “This spatial differentiation happens in biology naturally, but we demonstrated this process in vitro.”
According to Bruce Conklin, co-author of the study and a professor of medical genetics at UC San Francisco hundreds of thousands of pregnant women each year in the United States are exposed to drugs which could potentially harm their unborn fetuses. The most commonly reported birth defects are cardiovascular.
The researchers believe this early human heart model could be used as a drug-screening tool, so they exposed the differentiating cells to a drug called thalidomide, which famously caused a spate of birth defects in the 1950s and 1960s.
“We chose drug cardiac developmental toxicity screening to demonstrate a clinically relevant application of the cardiac microchambers,” said Conklin in a press statement.
After the tests, the researchers found that compared to normal heart tissue, tissue exposed to thalidomide triggered the microchambers to develop abnormally—they were smaller in size, had lower beat rates, and problems with muscle contraction.
For now, the researchers are working with heart cells, but said that in the future, this technology could be used to grow imitations of other organs.
