Plain Cells Turned into Beating Heart Cells to Fix Damage
Two studies published on Thursday show new ways to fix damaged hearts, one by turning structural heart cells into beating cells and another by restoring a primordial ability to regenerate lost tissue.
The two approaches need more work before they can be tried in humans, but they represent big steps forward in the new field of regenerative medicine.
And they show it may be possible to repair broken organs in the patient's body, instead of resorting to transplants or artificial devices.
In one study, a team at the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco made beating heart cells from more ordinary cells called fibroblasts.
Stem cell researchers know they can reprogram these ordinary cells by adding three or four genes to take them back to an embryonic-like state. Teams are working to fine-tune these so-called induced pluripotent stem cells or iPS cells.
Taking this approach a step further, Dr. Masaki Ieda and colleagues found the genes that, in a developing embryo, turn an immature cell into a beating heart cell or cardiomyocyte.
They used these three genes called Gata4, Mef2c, and Tbx5 to convert mouse heart fibroblasts — which provide structure but which cannot beat — into the beating cells.
"Scientists have tried for 20 years to convert nonmuscle cells into heart muscle, but it turns out we just needed the right combination of genes at the right dose," Ieda, now at the Keio University School of Medicine in Japan, said in a statement.
When they put these transformed cells into living mice, they converted into beating heart cells within a day, Ieda's team reported in the journal Cell.
CURING HEART FAILURE?
When patients suffer heart attacks, heart cells die as they become starved of oxygen. If enough dead tissue forms, patients suffer heart failure and eventually often die.
Scientists have been trying a variety of ways to regenerate this scar tissue, but patients with severe heart failure must use mechanical devices or hope for heart transplants.
Currently, 5 million Americans suffer from heart failure.
The approach will need a lot of refining, said Gladstone director Dr. Deepak Srivastava. "Direct reprogramming has not yet been done in human cells," he said. And it would be better to find a drug that can turn on the required genes; currently researchers usually use a virus to carry new genes into the cells.
For the second study, a team at California's Stanford University looked to amphibians called newts.
"Newts regenerate tissues very effectively," said Helen Blau of Stanford's Institute for Stem Cell Biology and Regenerative Medicine.
"In contrast, mammals are pathetic. We can regenerate our livers, and that's about it."
Also working in mice, Blau's looked for the reasons that amphibians can regenerate limbs and mammals cannot.
Other studies suggest that mammals have had to give up regeneration because the same process can also lead to cancer. A so-called tumor suppressor gene called retinoblastoma, or Rb, helps control this process in mammals.
"We hypothesized that maybe, during evolution, humans gained a tumor suppressor not present in lower animals at the expense of regeneration," Blau said.
They found a second gene called ARF is also involved.
When they blocked both Rb and ARF in mouse heart muscle cells, they started to grow and divide.
The key will be to control this process, so the cells do not overproliferate and form tumors, the researchers report in the journal Cell Stem Cell. They also want to see if this will work in other organs.