Researchers working to regenerate heart, nerve cells
Days ago, these building blocks of heart muscle had a different identity altogether: They were scar-forming cells that proliferate in the wake of a heart attack and weaken the organ's ability to pump blood.
Researchers at UT Southwestern and other institutions may have found a way to reverse the damage that patients sustain from heart attacks, traumatic brain injuries and other conditions.
They accomplish this by converting a less desirable type of cell, such as a scar-forming cell, into a highly desirable one, such as a nerve cell, using a process known as direct reprogramming.
Many scientists say direct reprogramming is a promising new approach to regenerative medicine — a field dedicated to curing disease by helping the body repair and regrow its own tissues.
In recent years, scientists have used the method to grow new brain cells, liver cells, pancreatic tissue and parts of the inner ear responsible for hearing loss.
Researchers hope to one day develop drugs that will enable patients' bodies to repair their own damaged organs, much the way a salamander can regrow its own heart and a python can double the size of its liver.
At UT Southwestern's new Hamon Center for Regenerative Science and Medicine, researchers are focused on cultivating heart and nerve cells.
The center, led by biologist Eric Olson, opened in May with a $10 million gift from the Hamon Charitable Foundation. Its areas of research include stem cells as well as direct reprogramming.
Olson hopes the center will help UT Southwestern attract top college graduates from around the U.S.
"Regenerative biology is one of the most popular majors," he says. "The center will give us a new tool to recruit some of the best students to Dallas."
Years of cardiac research
Olson's career-long interest in how a single cell develops into the trillions that make up the human body led to his lab's current work.
"I wanted to understand how specialized cells were formed and how large sets of genes turned on and off during development," he said.
After pondering what cell type to focus on, Olson settled on muscle cells, because muscles make up 40 percent of our body mass and turn on thousands of genes as they develop.
The idea was that a deep understanding of one particular system could be applied more widely. It could also help scientists gain insight into how diseases develop when errors creep into the process.
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Over the years, Olson's lab has uncovered several of the major genes that control muscle development.
Recent work from his lab has led to a promising approach to treating Duchenne muscular dystrophy, a congenital disease that causes muscles to progressively weaken and degenerate.
In the center's inaugural publication this month in the journal Science, Olson and his colleagues outlined a way to "edit" the gene abnormalities responsible for the disorder in a mouse and rectify the body's ability to grow healthy muscle.
Olson's lab extended its work into heart muscle cells in the early 1990s. At the time, Deepak Srivastava, then a postdoctoral researcher, was working in the lab.
"I was trained as a pediatric cardiologist and was interested in how the heart forms in the embryo and how that goes awry in human disease," says Srivastava, who now directs cardiac and stem cell research at the Gladstone Institutes and is a professor at the University of California San Francisco. The two went on to discover many of the genes that control heart development.
Using some of that research, Srivastava pioneered cardiac reprogramming several years later.
"We took the years of knowledge that our lab and other labs had developed about how nature normally makes a heart in the embryo and essentially redeployed those same methods in the adult heart," he says.
In a 2010 paper in the journal Cell, Srivastava showed that scar-forming cells known as fibroblasts could be converted into beating heart cells by adding just three ingredients. Those ingredients, proteins known as transcription factors, are master regulators that flip genes on and off. The genes involved are the same ones that direct heart formation in the womb.
In 2012, Srivastava and Olson, writing separate papers in the same issue of the journal Nature, showed that the process could be performed successfully in living mice.
Each group used a different combination of transcription factors to reprogram the cells, but both found that the technique improved heart function in the animals following a heart attack