Science on the SPOT: New Hope for Heart Repair
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More than 5 million people in the United States live with damaged hearts that make it difficult to walk and carry out other simple daily tasks. Pacemakers and drugs can help, but they don’t repair the heart muscle that has died as a result of a heart attack or clogged arteries.
Now, scientists in San Francisco say a more effective treatment might be on the way.
The researchers from the Gladstone Institutes, affiliated with the University of California-San Francisco, reported today that using a new genetic technique, they have succeeded for the first time in repairing, from within, the hearts of mice weakened by heart attacks.
“There are a variety of approaches we use right now to help people who are left with damaged hearts,” said Dr. Deepak Srivastava, senior author of the paper and director of cardiovascular research at the Gladstone Institutes, “but none of them actually get to the root of the problem, which is replacing that damaged heart muscle. And that’s where our focus has been.”
The scientists injected three genes into the hearts of research mice that had been given mild heart attacks. Within three months, the genes transformed non-beating cells in the heart into cells that looked and acted just like beating heart muscle cells. These new beating cells restored the heart’s ability to pump blood to the rest of the body.
Human hearts have billions of non-beating cells, which support the beating cells by forming the heart’s structure, Srivastava said. Mice have millions of these support cells too. When a heart attack happens, the support cells rush to the site of the damage and form scar tissue, which preserves the heart’s structure, but doesn’t help it pump blood.
“We’ve found a way to take these support cells that should normally never become muscle, and convert them into new muscle cells that actually integrate with the rest of the heart, contribute to the force that it generates, and allow us to regenerate the heart from within the organ itself,” said Srivastava.
Heart attacks and other heart disease kill 600,000 people each year. Many more survive, yet lead diminished lives. Some 5.7 million people live with damaged hearts that pump less blood, making it difficult for them to climb a flight of stairs or walk across a parking lot.
During a heart attack, clots block one or several coronary arteries and cut off blood flow. By rushing patients to the operating table and unclogging their arteries with catheters and stents, doctors are able to save all but 5 percent of victims who make it to the hospital.
“While we’ve been doing better at saving lives, each time we save a life the patient still loses some of their muscle,” Srivastava said. “So the number of people who are left with damaged hearts is actually growing, even though the number of people who die from heart attacks is getting smaller.”
Treatments for humans could be six to seven years away, he added. The next step will be to test the treatment on pigs. Scientists still need to figure out if cell reprogramming is safe for humans; how to deliver the genes into the heart, and how to produce enough new beating heart cells to repair a human – rather than a mouse – heart.
Nevertheless, the research is drawing the attention of other heart researchers.
“It’s a major discovery and certainly suggests a new approach to treat injury that previously had been thought to be irreversible,” said Dr. Eduardo Marbán, director of the Cedars-Sinai Heart Institute in Los Angeles.
Marbán said it’s been “a long-held dogma” that once scar tissue has formed in the heart, it can’t change into heart muscle. This finding in mice, and recent research by Marbán’s team on a small group of human patients, challenge that belief, he said.
Although the cell reprogramming research doesn’t involve stem cells, the Gladstone scientists used techniques that were discovered through stem cell research.
The scientists said their work was inspired by the discovery in 2007 that a few genes can transform an adult skin cell into a cell with the properties of a human embryonic stem cell. Researchers have been intensely interested in embryonic stem cells as a possible source of treatments for diseases like Parkinson’s because they can be coaxed to turn into virtually any type of cell in the body. But because embryonic stem cells are plucked from embryos left over from fertility treatments, and require the destruction of these embryos, their study has been controversial.
An alternative to embryonic stem cells came with the skin cell breakthrough five years ago. Then, Dr. Shinya Yamanaka, of the Gladstone Institutes and Kyoto University in Japan, inserted four genes that are present in embryonic stem cells into adult skin cells. The four genes reprogrammed the skin cells to become embryonic-like stem cells.
That led scientists to look for a way to transform one type of adult cell into another type of adult cell without the need to create stem cells at all.
“Yamanaka opened up the idea that adult cells weren’t permanently fixed,” said Srivastava. “That led us to ask whether or not we could convert one of these heart support cells into a heart muscle cell.”
Bypassing the creation of stem cells has several advantages. Though stem cells are versatile, when they’re introduced into the body they can behave as cancer cells and form tumors.
“It’s a dramatic and heady possibility that vindicates for the first time the idea that we might be able to harness truly regenerative medicine,” Marbán said.