FRIDAY, June 6, 2003 (HealthDayNews) -- By finding a way to keep smooth muscle cells dividing indefinitely, scientists have managed to fashion the first-ever human arteries from non-embryonic tissue in a laboratory.
The hope is that, eventually, these engineered human arteries will be available for routine use in coronary artery bypass surgery.
"This had never been done before. We took a task that was previously thought to be impossible and now put it in the realm of the possible," says Chris Counter, co-senior author of a paper detailing the discovery in the June 6 issue of EMBO Reports, the journal of the European Molecular Biology Organization.
Dr. Augustus O. Grant, incoming president of the American Heart Association and a professor of medicine at Duke University School of Medicine, says the feat is "without a doubt" a big step in heart research.
The search for a way to grow functioning human arteries has been on for quite some time.
The majority of coronary artery bypass grafting in the United States use blood vessels that have been harvested from somewhere else on the patient's body, usually from the legs. This is far from a limitless supply. Every year, some 100,000 people who need small-vessel grafts can't get them because their own veins are unsuitable.
"There are a lot of technical problems with securing appropriate vessels on the patients themselves," Grant says. "We need them."
One major obstacle has been the fact that smooth muscle cells, which form the outer wall of the vessels, have not survived long enough in culture to be able to develop a sturdy artery. "Before you can get a strong, sturdy vessel, the cells have undergone a large number of replications," Grant explains. "They become senescent. They become old."
The authors of the current study borrowed from cancer biology to ameliorate this problem.
Each cell chromosome has a section called a telomere. Each time a cell divides, the telomere shortens until, after a certain number of divisions, the telomere becomes so short it sends a signal to the cell to stop dividing. It's sort of the biological equivalent of planned obsolescence.
The authors of this study found a way (by inserting a gene called hTERT) to shut off a portion of one of the enzymes involved in the process of cell division. Shutting this down essentially made the cells immortal. Longer-living cells meant the scientists had time to construct their arteries. After the vessel walls were created, the lining of endothelial cells was added.
"The catch behind it is one had to make sure that you aren't creating cancerous cells because in essence this is one of the principles that cancer cells could use to propagate," Grant says. "That does not seem to have happened with these cells."
The authors estimate that it could take as long as a decade before these arteries are in routine use in operating rooms.
More long-term studies are needed to show the durability of these vessels. Scientists also want to make the entire vessel out of one person's cells (this artery was constructed out of cells from different people) and to do this many times over. Counter says his group has already submitted a paper for publication that repeats the accomplishment, using cells from one person.
Also, once real people involved, the researchers want to make sure the enzyme can be turned off again. "We want to erase all signs that we manipulated the cells before it goes back into the patient," Counter says.
More information
For more on coronary artery bypass surgery, visit the University of Michigan or the American Heart Association.
