Scientists at the Gladstone Institutes, a research foundation affiliated with the University of California-San Francisco, reported today that they have succeeded for the first time in creating beating heart cells from other types of adult cells.
The breakthrough offers new hope to the more than 5 million people in the United States who have survived heart attacks that one day their damaged hearts could be repaired.
When a person suffers a heart attack, the heart sustains damage than can permanently inhibit its function. Devices like pacemakers, and drugs like beta blockers, can keep the heart going, but not restore it to its full capacity – something that only a heart transplant can achieve today. But only about 2,000 hearts are available for transplants in the United States each year.
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“This discovery opens a door to think about a different approach, which is to take cells that are already within a damaged heart and convert them from just a simple structural cell that’s not beating into a cell that’s beating like its neighbors,” said Dr. Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease and a member of the research team.
“That can help the heart squeeze better and maybe avoid the need for transplantation.”
The new research appears in the August 6 edition of the journal Cell and was led by Masaki Ieda.
“It’s a major step forward in regenerative medicine,” said Dr. Ira Cohen, director of the Institute for Molecular Cardiology at Stony Brook University in New York, who wasn’t involved in the research. “It represents a novel approach to replacing heart cells.”
Research bypasses stem cells
The new research represents the first time that scientists have succeeded in creating beating heart muscle cells from adult cells that are not stem cells. Researchers had previously created heart muscle cells from both embryonic and adult stem cells.
Embryonic stem cells, and adult cells that have been made to act like embryonic stem cells, are referred to as being “pluripotent” because they have the unique ability to transform into many different types of cells. Scientists hope that one day stem cell research can lead to cures for a wide host of diseases, from diabetes to Parkinson’s. Stem cells that are pluripotent give researchers great flexibility, but they also could cause the wrong type of cell, or even a tumor, to end up in a patient’s heart. In bypassing stem cells, the new research avoids these potential problems, said Cohen.
The new research follows in the footsteps of a groundbreaking discovery by scientist Shinya Yamanaka, of the Gladstone Institutes and Kyoto University. In 2007, Yamanaka found that adult skin cells can be reprogrammed to become embryonic-like stem cells. Yamanaka and his team inserted four genes that are present in embryonic stem cells into adult cells. The four genes reprogrammed the adult cells to become embryonic-like stem cells.
The discovery, a major medical advance, offered a new way for stem cell research to proceed without many of the ethical and religious debates over the use of embryonic cells that had previously surrounded it.
And it also revealed to scientists that “in fact an adult cell could be induced to change so much, which we didn’t think was possible before,” said Srivastava.
Three genes did the trick
In the latest research, Srivastava and his team applied Yamanaka’s technique, but instead of seeking to create stem cells, they set out to bypass stem cells altogether. They took 15 genes from heart muscle cells and inserted them into adult cells called fibroblasts, which are found in the body’s connective tissue. They used fibroblasts from mice hearts and tails.
The researchers then looked for signs that the fibroblasts were becoming like heart muscle cells. Once they verified that heart muscle cells had been produced, they removed the genes one by one until they were left with the three genes that were necessary, but sufficient, to make the reprogramming happen.
The beating heart cells appear green.
Heart attacks are the number 1 cause of death in the United States, killing half a million people each year. This week’s research is an early step toward what one day could become a new treatment to repair the heart. Under one potential scenario, Srivastava said, rather than inserting genes into a patient’s heart, a doctor might deliver a therapeutic substance to the heart through a stent – without surgery – to transform non-beating heart cells into new beating heart cells.
To date, gene therapy has run into problems because introducing new genes into the human body can cause cancer.
One of the questions that the new research doesn’t answer is whether this technique would be able to generate enough heart muscle cells – which are called cardiomyocytes – to repair a damaged heart, said Cohen.
“You’re talking about replacing 1 billion cardiomyocytes,” he said. “How do you generate that many cells? How do you guarantee they’re healthy? How do you deliver them healthily? And how do you guarantee they stay there?”
Cardiac stem cells offer another possible treatment
Other approaches to regenerating heart cells also are being investigated.
Two clinical trials are underway in the United States to study the possibility of repairing the heart by giving patients an infusion of their own heart stem cells. Results of one of the trials, which is being carried out at the Cedars-Sinai Medical Center in Los Angeles, are due at the end of 2010, said researcher Rachel Smith, from the hospital’s Heart Institute.
In the so-called CADUCEUS trial, researchers take a few snips of the heart during an outpatient biopsy, then culture the tissue for three to four days to increase the number of stem cells. Close to 25 million cardiac stem cells are then infused into the heart through a catheter that goes into the blood vessel that feeds the organ.
“In a pig model, giving that equivalent dose of cells actually caused the area of damage in the heart to shrink,” said Smith.
Earlier this year, a team at Stanford University reported that they had reprogrammed an adult skin cell to become a neuron-like cell. And in 2008, scientists reprogrammed one type of cells found in the gut – exocrine cells – into another type, endocrine cells.
“This paper follows on the heels of those two discoveries,” said Kriegstein, “and it provides fascinating potential applications.”
This beating heart cell video was produced by the Gladstone Institutes' researchers.
More video:
Watch QUEST TV's segment about stem cell research, called Stem Cell Gold Rush.
Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease, co-authored the new paper.