Even through a microscope there's no mistaking the rhythmic beating. The living heart cells were actually created in a Bay Area lab. And they've helped researchers unlock the secrets of how a heart becomes a heart.
"It helps to have a blueprint to know what switches exist, how they're connected, and what they turn on or shut off," said Benoit Bruneau, Ph.D., associate director of the Gladstone Institute of Cardiovascular Disease. Bruneau and his team at San Francisco's Gladstone Institutes set out to map the genetic switches locked inside the DNA of embryonic stem cells to see how a stem cell becomes a heart cell, "And so what these epigenetic modifications are doing is they're setting the right switches to turn genes on or off so a heart cell, in this case, gains its heart identity."
To begin, researcher Jeffrey Alexander, Ph.D., had to coax millions of embryonic stem cells taken from mice into becoming beating heart cells. The process, done in a petri dish, uses growth factors that mimic the environment in the womb. Alexander notes that it's not always a precise science, joking "You know, my weekends sometimes would hinge on whether I came in and saw beating cells or not."
Once the team had enough of the beating cells, known as cardiac myocites, they began watching them as they grew and developed, painstakingly extracting their DNA and cataloguing the genetic changes. A process made possible only recently by the development of powerful new gene sequencing technology, "The human genome, announced 10 years ago to great fanfare, cost three billion dollars to sequence one individual's DNA," Bruneau said. "Now we can do the same person's DNA in a week for $3,000." Still, it took massive networks of computers to organize the data into a color coded genetic blueprint, detailing the creation of a heart cell.
While having a genetic blueprint might conjure up images of growing hearts, the more immediate impact might actually be repairing them, or perhaps even heading off birth defects in babies, before they're even born, "We potentially could," Bruneau said. "And part of the attraction to understanding this blueprint, especially this type of blueprint, is that it's very amenable to drug type interventions."
The Gladstone team now hopes to study the DNA of patients born with congenital heart disease. The goal was to identify the genetic disruption that caused their heart defect in the first place, and possibly identify treatments that could turn the switches back to normal; changing the lives of some 35,000 babies born with heart defects in the U.S. every year.
Bruneau's team says early targets of this technology might be the most common forms of heart defects such as arrhythmia, irregular heartbeat, or ventricular defects which cause holes in the heart chambers.
Written and produced by Tim Didion