Scientists have developed beating heart tissue from stem cells, an advance that could help screen for drugs likely to generate cardiac birth defects and guide decisions about which drugs are dangerous during pregnancy.
University of California Berkeley researchers, in collaboration with scientists at the Gladstone Institutes, have developed a template for growing beating cardiac tissue from stem cells, creating a system that could serve as a model for early heart development and as a drug-screening tool to make pregnancies safer.
In experiments published in the journal Nature Communications, the researchers used biochemical and biophysical cues to prompt stem cells to differentiate and self-organise into micron-scale cardiac tissue, including microchambers.
“We believe it is the first example illustrating the process of a developing human heart chamber in vitro,” said Kevin Healy, a UC Berkeley professor of bioengineering.
“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,” Healy said.
To test the potential of the system as a drug-screening tool, the researchers exposed the differentiating cells to thalidomide, a drug known to cause severe birth defects.
They found that at normal therapeutic doses, the drug led to abnormal development of microchambers, including decreased size, problems with muscle contraction and lower beat rates compared with heart tissue that had not been exposed to thalidomide.
“We chose drug cardiac developmental toxicity screening to demonstrate a clinically relevant application of the cardiac microchambers,” said Dr Bruce Conklin, a senior investigator at the Gladstone Institute of Cardiovascular Disease. “Each year, as many as 280,000 pregnant women are exposed to drugs with evidence of potential foetal risk. The most commonly reported birth defects involve the heart, and the potential for generating cardiac defects is of utmost concern in determining drug safety during pregnancy,” Conklin said.
The scientists mimicked human tissue formation by starting with stem cells genetically reprogrammed from adult skin tissue to form small chambers with beating human heart cells. The undifferentiated stem cells were then placed onto a circular-patterned surface that served to physically regulate cell differentiation and growth. By the end of two weeks, the cells that began on a two-dimensional surface environment started taking on a 3D structure as a pulsating microchamber. Moreover, the cells had self-organized based upon whether they were positioned along the perimeter or in the middle of the colony.
Compared with cells in the centre, cells along the edge experienced greater mechanical stress and tension, and appeared more like fibroblasts, which form the collagen of connective tissue. The centre cells, in contrast, developed into cardiac muscle cells.