Sci. Aging Knowl. Environ., 11 May 2005
Heart, Heal Thyself
Researchers turn on possible heart-repair mechanism
Much as children eventually lose interest in their Star Wars action figures, heart cells are supposed to grow out of the ability to divide. But a new study shows that with the right chemical coaxing, adult heart cells from rodents can duplicate, at least in the lab dish. If the results hold true for humans, such youthful cells might eventually allow patients to refurbish cardiac tissue sapped by heart disease.
Scientists have long thought that adult heart cells can't divide. Because of this lethargy, the organ can't rebuild itself after an injury, such as that triggered by a heart attack. One experimental measure for repairing this damage involves infusing stem cells from bone marrow into heart disease patients. The procedure strengthened the heart, researchers found, but uncertainty remains about whether the cells formed new tissue or whether they released compounds that fortified existing cells, says cardiologist Andre Terzic of the Mayo Clinic College of Medicine in Rochester, Minnesota. Cell biologist Felix Engel of Harvard Medical School in Boston and colleagues decided to pursue a different strategy based on the observation that heart cells split rapidly during fetal development, a capacity they lose shortly after birth. The researchers wanted to determine what curtails division and figure out whether they could release this restraint in adult cells.
The team suspected that a protein called p38, which drives cells throughout the body to specialize, is what halts division. Engineering fetal rat heart cells to produce extra p38 slashed the amount of cell division. Conversely, a compound that blocks p38 activity boosted duplication by nearly three times in normal cells. In fetal mice modified to generate overactive p38, heart cell division fell by nearly 80% compared with normal rodents. And cells from newborn mice lacking the p38 gene duplicated at higher rates than did controls.
The real test, however, was whether the researchers could spur adult cells to split. They removed heart cells from young adult rats and prodded them with growth-inducing molecules. Adding a p38 blocker doubled the amount of cell division in the cultures. A protein framework allows heart cells to contract, and fetal cells temporarily disassemble the structure when they divide. Duplicating adult rat cells follow suit, the team observed. The researchers are now testing whether they can fire up cell division in a living animal, Engel says: "It gives hope for an alternative method to stem cells to treat heart failure."
"It's the first demonstration of the ability to drive division in adult heart cells," says developmental biologist Ian Scott of the University of California, San Francisco. Researchers have battled over whether the heart hosts stem cells that could be induced to initiate repair, he says, but this paper sidesteps that controversy by showing that normal cells might be able to do the job. Cell and molecular biologist Doris Taylor of the University of Minnesota, Twin Cities, says that the study provides "the first good evidence that it [cardiac regeneration] is something that we might be able to control." Future work might reveal whether a little immature behavior is good for the heart.
May 11, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150