Scientists Engineer Breathing Lung in Rats

Jessica Berman | 25 June 2010| VOA|

A team of U.S. scientists has built the first artificial lung using natural cell-growth processes and implanted the organ successfully in rats. Experts say the achievement is an important first step in creating a fully-functional, breathing lung to replace a diseased or damaged organ.

Living lung: A rat lung, grown from the scaffold of an old lung seeded with healthy cells, is mechanically ventilated in a bioreactor. At the end of a week, the lung was transplanted into a rat, and was able to exchange gases, as a normal lung would, for two hours. Credit: Thomas Petersen and Laura Niklason, Yale University

In the experiment, researchers at Yale University in New Haven, Connecticut took the lungs from four rats and stripped them of their cells using detergents and enzymes, leaving behind only a delicate white matrix or scaffold.

They immersed this scaffold in a large beaker, or bioreactor, filled with a solution of growth factors and other proteins that normally support fetal lung development in the womb. The scientists then placed lung cells from rats on the scaffold. Under the womb-like conditions, the cells grew into a well-defined mass of functioning lung tissue covering the matrix.

Laura Niklason, a professor of anesthesiology and biomedical engineering at Yale University in New Haven, Connecticut, led the study.

In an interview via Skype, Niklason says researchers implanted these naturally engineered lungs back inside the rodents, where they began breathing, exchanging oxygen and carbon dioxide almost as efficiently as natural lungs.

“We’re really trying to use all the cues from nature that we can,” she said. “You know we’re trying to use the correct lung matrix and we’re trying to use a culture environment that’s as much like lung development in the womb that we can. And I think that by listening to nature, I think it’s enabled us to make quite a bit of progress.”

Between 45 minutes and an hour-and-a-half after they were implanted, Niklason says the engineered lungs formed clots and stopped functioning.

Edward Morrisey is scientific director at the Pennsylvania State University Institute for Regenerative Medicine.

Morrissey praises the first-time achievement by Niklason and her colleagues in creating the breathing lung, which the investigators describe in their published report.

“I think it’s a really beautiful proof-of-concept paper showing that an organ such as the lung, which is a very complex organ – obviously it has to be attached to both the circulatory system as well as the air handling system, the upper airways, the trachea and such, that you can actually generate one of these things,” he said.

Nearly a dozen specialized cells were used to create the fabric of lung tissue in the bioreactor before the organ was implanted in the rats.
Without any coaxing, the cells seemingly knew where to grow on the scaffold, according to Daniel Weiss, a pulmonology and critical care specialist at the University of Vermont. Weiss, too, believes the successful experiment is noteworthy because the lung is such a complex organ made up of many different types of cells.

“They have to organize themselves, where they sit next to each other, and next to other different types of cells. And at the end of the day, the lung is a gas exchange organism [organ]. It’s how you breathe. And so this is the ultimate functional outcome. And for someone to be able to do this in a model system outside the body is really phenomenal,” said Weiss.

The lung experiment raises the prospect that one day, people with potentially fatal lung diseases, such as cancer and emphysema, could be saved with naturally-engineered replacement lungs.

But Yale University’s Laura Niklason says it’s likely to be at least 20 years before such engineered lungs are ready for human implantation.

A paper describing the creation of the first lab-engineered lung tissue is published this week in the journal Science.