Researchers have taken the first steps in developing a mini heart from stem cells. The tiny structures, which actually beat like living hearts, could help scientists determine if new heart drugs are safe for the heart, and — importantly — could help make pregnancies safer by screening for drugs that can cause cardiac birth defects.

Scientists from the University of California, Berkeley, in collaboration with scientists from Gladstone Institutes, used biochemical and biophysical cues to nudge immature adult stem cells to differentiate and organize into cardiac tissue, including microchambers.

"We believe it is the first example illustrating the process of a developing human heart chamber in vitro," said UC Berkeley professor Kevin Healy. "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."

In the past, researchers have used stem cells to grow beating heart muscle as well as tiny tubes that pumped, but they couldn't create the type of chambers found in hearts. For the current research, Berkeley scientists found if they carved microscopic circular pits in the bottoms of petri dishes, the cells developed into microscopic hollow chambers.

Pluripotent stem cells — adult stem cells that have been genetically manipulated to resemble embryonic stem cells — were placed on the pitted surface which regulated their growth by confining them to the small pits. Within two weeks, the cells started developing into 3D structures as pulsating microchambers.

In addition, the cells organized themselves depending on where they were placed. Cells on the outside seemed to be more like fibroblasts, which form the collagen of connective tissue, and the center cells developed into cardiac muscle cells. By the end of two weeks, the cells started taking on a 3D structure as a pulsating microchamber.

"This spatial differentiation happens in biology naturally, but we demonstrated this process in vitro," said study lead author Zhen Ma, PhD, a U.C. Berkeley postdoctoral researcher in bioengineering. "The confined geometric pattern provided biochemical and biophysical cues that directed cardiac differentiation and the formation of a beating microchamber."

The researchers tested the micro heart's ability to screen for harmful drugs by exposing the cells to thalidomide, a drug known to cause severe birth defects. When compared to micro heart tissue that had not been exposed to thalidomide, they found that even in normal doses, the drug led to abnormalities, such as structures that were smaller and had problems contracting.

"We chose drug cardiac developmental toxicity screening to demonstrate a clinically relevant application of the cardiac microchambers," said researcher Dr. Bruce Conklin, M.D. "Each year, as many as 280,000 pregnant women are exposed to drugs with evidence of potential fetal 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."

According to the March of Dimes, almost one in 100 babies is born with a congenital heart defect.