The Human Heart
Anterior (frontal) view of the opened heart. White arrows indicate normal blood flow.

They have already been dubbed “master” heart cells, and hold the promise of treating patients with serious cardiovascular disease: Three US research groups claim that they can produce stem cells that give rise to different tissues found in the mammalian heart.

Each team has identified cardiovascular “precursor” cells from cultures of mouse embryonic stem cells (ESCs). It is very likely that these versatile cells will also be found in the embryonic human heart, the researchers say, raising hopes of one day repairing and “rejuvenating” damaged hearts by growing these embryonic stem cell lines in a lab.

Two of the groups, one led by Kenneth Chien of the Massachusetts General Hospital in Boston, the other by Gordon Keller of Mount Sinai School of Medicine in New York, say their precursors give rise to three types of cells in the heart. Cardiac muscle cells can be grown, as can the smooth muscle that makes up the blood vessels that supply the heart, and crucial endothelial cells that line the coronary blood vessels, they say.

The third team, led by Stuart Orkin of the Children’s Hospital in Boston, has identified precursors for cardiac and smooth muscle.

Being able to rebuild both cardiac muscle and blood vessels may be important for repairing hearts ravaged by cardiovascular disease. “Where there’s damage, there’s damage to more than one cell type,” notes Orkin.

Muscle cells

Cell therapies for failing hearts have been hampered by the lack of a suitable stem cell. Some cardiologists have tried injecting bone marrow stem cells into patients’ coronary blood vessels or heart muscle. But there is no good evidence that injected marrow cells can differentiate into new heart tissue.

Trials with muscle cells taken from the legs have been even less successful, with some patients developing dangerous arrhythmias – where the heart does not beat to a correct rhythm.

These newly found precursor cells, discovered in culture, seem to correspond to cells present in the mouse embryo, which give rise to heart tissue during normal development, the three teams say. Mimicking natural developmental processes in culture boosts the prospects of successful cardiac repair, they argue.

“This is the beginning of science-based cardiovascular regenerative medicine,” claims Chien.

Clinical trials

The researchers are now trying to work out if they are each studying cells on the same developmental pathway. “It’s hard to be absolutely dogmatic about that,” says Orkin, because each group identified their cells using different cell-surface marker molecules.

And each team wants to repeat the experiments with human ESCs, so that they can begin moving towards clinical trials. “We are following up very quickly with human cells,” says Keller.

The stem cell company, Geron of Menlo Park, California, also plans to treat heart disease using cells derived from human ESCs. It is concentrating on generating precursors for cardiac muscle, rather than “master” heart cells.

Geron’s CEO, Tom Okarma, says the company already has promising results from experiments in rodents with damage following a simulated heart attack. Okarma also hopes to avoid problems with immunological rejection by generating “tolerance” using immune cells derived from the same ESC lines.

Stem cells may help repair damaged 1) ___ after a heart attack. A study, done on mice, shows that stem cells play a limited, but significant role in 2) ___ damaged hearts. However, it remains unclear whether it is heart cells that are doing the repair, or cells from elsewhere in the 3) ___. Richard Lee and colleagues of the Harvard Medical School genetically engineered mice so their heart muscle cells could be stained with a fluorescent 4) ___. Around 80% of the heart 5) ___ cells in young mice picked up the stain. As the mice 6) ___, this level remained the same, which demonstrates that heart muscle cells are not normally replaced in life. However, when heart attacks were induced in the mice, the number of stained cells dropped to 70%, suggesting that new muscle cells are formed in response to injury. The study showed that the adult mouse 7) ___ has a limited ability to repair itself. The mechanism to activate cardiac 8) ___ is present, but it’s inadequate. This could be, because mammals don’t have enough [heart] stem cells? There are other theories as well. We need to understand what is holding the system back, so that we can devise a strategy to turn that brake off. Heart stem cells were first discovered last year. It’s not clear if this team has identified heart stem cells in the mice. Are they pre-existing immature cardiac muscle cells? Or are they [stem cells] from the heart or elsewhere in the body? Source: Nature Medicine (DOI: 10.1038/nm1618).

ANSWERS: 1) tissue; 2) repairing; 3) body; 4) protein; 5) muscle; 6) aged; 7) heart; 8) regeneration