They have already been dubbed 鈥渕aster鈥� 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 鈥減recursor鈥� 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 鈥渞ejuvenating鈥� 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.
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The third team, led by Stuart Orkin of the Children鈥檚 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. 鈥淲here there鈥檚 damage, there鈥檚 damage to more than one cell type,鈥� 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鈥� 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 鈥� 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.
鈥淭his is the beginning of science-based cardiovascular regenerative medicine,鈥� claims Chien.
Clinical trials
The researchers are now trying to work out if they are each studying cells on the same developmental pathway. 鈥淚t鈥檚 hard to be absolutely dogmatic about that,鈥� 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. 鈥淲e are following up very quickly with human cells,鈥� 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 鈥渕aster鈥� heart cells.
Geron鈥檚 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 鈥渢olerance鈥� using immune cells derived from the same ESC lines.
Journal references: Cell (DOI: 10.1016/j.cell.2006.10.028 & DOI: 10.1016/j.cell.2006.10.029) Developmental Cell (vol 11, p 723)
