New Vessels From Old Cells

October 1, 2005

 

Coronary bypass surgery is a proven lifesaver for millions of Americans each year, but a nagging problem remains. Some 100,000 of the 1.4 million Americans each year who need such small-vessel grafts to replace clogged or damaged arteries don't have strong enough vessels to use as donors. Also, artificial vessels won't work in many cases because the patient needs smaller implants, and small, artificial vessels become clogged.

Now, Duke biomedical engineers have shown that they can generate healthy new vessels using cells from elderly patients--a group that is especially prone to such problems. The laboratory experiments constitute only a proof of principle so far, says lead researcher Laura Niklason. But within five to ten years, patients could be receiving arteries grown in the lab from their own cells.

Niklason and her colleagues described their results in an article in the June 18 issue of the journal Lancet. They took blood- vessel cells from four elderly men with heart disease, treating the cells to, in essence, make them "ignore" their age. The cell treatment overcomes a problem with using cells from the elderly as donor cells for growing arteries. As such cells have divided over the person's lifetime, they have gradually eroded away marker molecules from the tips of their chromosomes that signal how many times a cell has divided. Such gradual loss is a kind of protective biological alarm clock that tells cells when they have divided enough times that they should stop, to avoid passing on age-accumulated malfunctions to their progeny cells.

Niklason's colleague Christopher Counter, however, had figured out a way to alter cells genetically to produce an enzyme that halts the ticking of this molecular clock. The aged blood-vessel cells then could be induced to multiply indefinitely to form lab-grown vessels.

To create the new arteries from the altered donor cells, the researchers impregnated the cells into a tube of a biodegradable, spongelike polymer. They then pulsed a vitamin and nutrient solution through the tube, imitating the conditions for artery growth. Once the cells had grown into an artery-like structure, the researchers added the kinds of endothelial cells that line the inside of arteries. The resulting lab-grown arteries are still not strong enough to be implanted into humans, says Niklason. However, she says, fine-tuning the growth technique should overcome such problems and lead to arteries suitable for clinical testing.