Yale scientists take apart and rebuild a rat’s lung, early step to future lung regeneration

Scientists grow a rat lung in the laboratory

WASHINGTON — It’s an early step toward one day building new lungs: Yale University researchers took apart and regrew a rat’s lung, and then transplanted it and watched it breathe.

The lung stayed in place only for an hour or two, as the scientists measured it exchanging oxygen and carbon dioxide much like a regular lung — but also spotted some problems that will take more research to fix.

Still, the work is a step in the science fiction-sounding hunt for ways to regenerate damaged lungs — although lead researcher Dr. Laura Niklason cautions that it may be 20 or 25 years before a build-a-new-organ approach is ready for people.

The work was reported online Thursday in the journal Science.

Nearly 400,000 people die of lung diseases each year in the U.S. alone, according to the American Lung Association, and lung transplants are far too rare to offer much help.

But how to replicate these spongy organs? Niklason’s team stripped an adult rat’s lung down to its basic structural support system — its scaffolding — to see if it’s possible to rebuild rather than starting completely from scratch.

First, they essentially washed away the different kinds of cells lining that lung. It gradually faded from a healthy red to a white structure of mostly collagen and other connective tissue that maintained the shape and stretchiness of the original lung, even the tubes where airways would be.

This scaffolding is like a universal donor that shouldn’t pose rejection problems, said Niklason: “Your collagen and my collagen are identical.”

The researchers put the lung scaffolding into a bioreactor, an incubator-style container designed to mimic the environment in which fetal lungs develop, with fluid pumping through them.

Then they injected a mixture of different lung cells taken from a newborn rat. In the bioreactor, those cells somehow migrated to the right spots and grew air sacs, airways and blood vessels.

In short-term implants in four different rats, engineered lungs replaced one of the animals’ native lungs and proved 95 percent as efficient at exchanging oxygen and carbon dioxide, Niklason said.

However, among the problems she spotted were small clots that formed inside the engineered lung, a sign that the new cells hadn’t grown a thick enough cover in some places.

The biggest challenge: For this approach ever to work without a person’s body rejecting the new tissue, scientists would need to use a recipient’s own cells, Niklason explained. But there isn’t a way yet to cull the kind of personalized stem cells that would be needed, meaning stem cell research must improve first, she said.

This overall approach also worked in a 2008 University of Minnesota experiment that grew a beating rat heart, and Minnesota researcher Dr. Doris Taylor welcomed the Yale lung work.

Separately in Science, a Harvard University team coated a flexible chip with layers of living lung cells, creating a laboratory tool that mimics some of the action of a breathing human lung. The goal: To replace some of the animal studies needed to test how lungs react to environmental toxins or inhaled drugs.

Online: www.sciencemag.org