Scientists Discover Way to Grow Blood Vessels in Lab

Scientists at the Massachusetts Institute of Technology have produced for the first time artificial blood vessels from cells grown in the laboratory.

The living blood vessels hold great promise for replacing small vessels that have been damaged by diabetes, blood vessel diseases or physical injury, the scientists said.

As many as 300,000 people each year in the United States could benefit from small blood vessel replacements if they should become widely available.

Such availability could come only after successful tests in animals and humans, a process that may take at least five years.

The development of a living replacement vessel could provide an important new tool for surgeons treating limb damage. Dacron tubes are now routinely used to replace large blood vessels that have been damaged, but Dacron does not work for vessels smaller than about a quarter of an inch in diameter, such as those found in the limbs.

When a Dacron tube that small is used, blood clots form and the tube becomes blocked, usually within an hour. Saphenous, or superficial, veins from the leg are now used for small vessel repairs, but as many as a quarter of prospective patients do not have a usable saphenous vein.

Crispin Weinberg and Eugene Bell of MIT report in today’s issue of the journal Science that they developed the living blood vessels by using techniques similar to those they had previously used to prepare artificial skin.

The key to both developments was their discovery that certain types of cells can cause a gel of collagen--a fibrous tissue found in bone, cartilage, and connective tissue--to contract by a factor of 10 to 20, forming a tough, tissue-like lattice.

In their earlier work, this lattice served as a base on which were scattered a small number of skin cells. The cells were then allowed to proliferate in an incubator until they covered the entire surface. Skin prepared in this manner can be used to cover wounds.

Physicians are now conducting clinical trials of this artificial skin at several burn centers around the country.

The manufacture of the artificial blood vessels proceeds in the same manner, Weinberg said in a telephone interview.

He and Bell used smooth muscle cells from the blood vessels of cows to contract the collagen gel. The cells and the collagen are cast around a thin cylinder called a mandrel.

After the collagen has contracted, a process that takes a few days, a sleeve of Dacron polyester mesh is slipped over the lattice and an outer layer of collagen and a different type of cells called fibroblasts is cast over it. Another week to two weeks is required for this layer to contract.

4 to 6 Weeks

The lattice is then removed from the mandrel and endothelial cells from the interior of cow blood vessels are scattered over the interior. They are allowed to proliferate until they completely cover the interior. “The complete process, from the initial casting to the harvesting of the completed vessel, takes four to six weeks,” Weinberg said.

The opaque, white three-layered structure of the completed vessel “grossly resembles a muscular artery, except for the Dacron mesh,” Weinberg said. The interior even secretes a substance called prostacyclin that prevents blood from clotting on the surface of vessels, as well as other hormones.

The principal differences between natural and artificial vessels are that the artificial vessels do not contain elastin, an important arterial connective tissue protein, and that the densities of collagen and smooth muscle cells in the artificial artery are less than a quarter of the densities in a normal blood vessel--which might suggest that the vessels are rather fragile.

Nonetheless, preliminary tests have shown that the artificial blood vessels can withstand pressures at least twice those that might be encountered in the body.

Durability Factor

“If the model is sufficiently durable after implantation in animals and the immunological barrier to (the foreign material) can be overcome,” the pair wrote, “then models constructed with human cells might serve as living vascular prostheses for small-caliber arteries.”

Physicians studying the problems with plastic vessels have thought that the blockage was caused by clotting triggered by the surface of the conventional plastics. Many chemists have created plastics that resist clot formation, but small vessels made from the new plastics also became blocked.

After much study, Donald Lyman of the University of Utah concluded that the major problem was that the plastic tubes are much less flexible than blood vessels. Blood vessels normally expand and contract with each beat of the heart, but the plastic replacements did not.

This difference in flexibility, he found, triggered the growth of muscle cells at the juncture between the normal blood vessel and the plastic replacement. The proliferation of these cells eventually blocked the replacement.

Lyman created plastics that were as flexible as the blood vessels and used them to make tubes. He has found in preliminary experiments that these vessels do not become blocked even after long periods. These new plastic vessels are now being studied in humans at several centers.

The MIT vessel might prove superior to Lyman’s if it could truly be integrated into normal blood vessels, but both types may find wide use.