A Duke University Medical Center researcher, in experiments conducted largely in the MIT laboratory of a pioneer in tissue engineering, has grown entire blood vessels from a few cells collected from pig arteries.
The new arteries, when implanted in the animal, worked like the real thing.
Calling these results a significant advance in the effort to someday create replacements for diseased body parts in humans, the report of the work by Laura Niklason and colleagues appears in the April 16 issue of Science. The research was done primarily in the laboratory of Robert S. Langer, the Germeshausen Professor of Chemical and Biomedical Engineering.
"We are very excited that after many years, we have produced a bioengineered tissue that appears functional in animals," said Niklason, an anesthesiologist and bioengineer at Duke.
Professor Langer and Harvard surgeon Dr. Jay Vacanti have invented unique synthetic polymer systems that can be used as scaffolding for growing tissue and organs. By fusing mammalian cells with synthetic polymers, Professor Langer and colleagues have created cartilage, tendons, bone and nerves, and have even formed a tube lined with working intestinal cells in animal models. Artificial skin made with this approach is now approved by the FDA. An artificial liver is in the works.
In the experiment described in Science, Dr. Niklason placed smooth muscle cells from pig arteries within the matrix of a tube fashioned from a polymer. She then placed the tube in a bioreactor that pulsed nutrients and vitamins around and through the growing vessels, mimicking the environment of the womb. Previous experimental tissues have been grown in static, non-pulsing systems.
After about two months, the smooth muscle cells had proliferated and the scaffolding had mostly dissolved. Dr. Niklason then added endothelial cells, which line the interior of blood vessels. A week later, the now-complete arteries -- which looked and behaved identical to native vessels -- were implanted into the adult pigs that provided the cells.
Arteries that were grown in the bioreactor, as well as those grown in a static environment, were monitored in the pigs for four weeks. The arteries grown in the bioreactor stayed open and functional for the entire four weeks, while those grown without the pulsing action began to show signs of clotting after three weeks.
'MAJOR ADVANCES' POSSIBLE
"This is a very innovative approach to tissue engineering that will set the stage for major advances," Professor Langer said. "Most tissue culture systems are static. Dr. Niklason has taken it one step farther and made a system that acts like a living body. The bioreactor she developed demonstrates that we can begin to grow cells and tissues in a more physiological way outside the body."
However, Drs. Niklason and Langer pointed out that this procedure is still a long way off for use to replace, for instance, diseased veins around human hearts. Smooth muscle cells from pigs are relatively easy to grow in culture outside the body while similar human cells are extremely difficult to grow, they said.
In addition to Dr. Niklason, a former MIT research affiliate, and Professor Langer, the authors of the Science study are Dr. Jinming Gao, a former postdoc at MIT now at Case Western Reserve University, Cleveland; Dr. William Abbott and Dr. Stuart Houser of Massachusetts General Hospital; Dr. Karen Hirschi of the Baylor College of Medicine; and Dr. Robert Marini, assistant director of the Division of Comparative Medicine at MIT.
This work was funded by the National Institutes of Health and the Foundation for Anesthesia Education and Research.
A version of this article appeared in the April 21, 1999 issue of MIT Tech Talk (Volume 43, Number 27).