A rat lung today, a human one tomorrow?

A team led by School of Medicine professor Laura Niklason succesfully grew a rat lung in a laboratory. Niklason heralded 2010 as “the year of the lung.”
A team led by School of Medicine professor Laura Niklason succesfully grew a rat lung in a laboratory. Niklason heralded 2010 as “the year of the lung.” Photo by Lindsay Gellman.

The starfish, known for its ability to regenerate damaged tissue quickly, may have been upstaged this summer by the humble lab rat.

A team led by anesthesiology and biomedical engineering professor Laura Niklason grew an artificial lung from harvested rat lung tissue and successfully implanted the new lung into a live rat. The team published its findings in the June 24 issue of Science Express.

“I think 2010 will go down as the ‘year of the lung,’ ” Niklason said. “Prior to 2010, hardly anyone was doing research in lung regeneration; now it’s all the rage.”

Niklason’s team used a new tissue engineering method known as decellularization — a method of removing a tissue’s individual cells while leaving its structure intact — pioneering the technique’s use in the treatment of lung disease. Niklason said the researchers treated the extracted adult rat lungs with a detergent chemical. The detergent removed most lung cells, leaving the tissue’s airways, blood vessel network and fibrous architectural structure, or extracellular matrix, intact.

With this framework in place, Niklason said her team applied harvested lung cells grown in vitro from newborn rats to the existing framework.

Niklason said the findings were “remarkable”: The cultured cells successfully distributed themselves to appropriate locations on the framework, resulting in healthy adult rat lung tissue.

“We were the first to report that it’s possible to make a tissue in vitro that can exchange gas,” she said.

The lungs efficiently exchanged carbon dioxide waste and delivered fresh oxygen to the blood — the essential function of natural lungs, Niklason said.

When implanted in adult rats for short time intervals (45 to 120 minutes), the bioengineered lungs allowed for a 95 percent rate exchange of carbon dioxide and oxygen in comparison with natural lungs, she added.

The team’s findings could forecast potential applications in human medicine, such as replacing diseased human lungs with lab-grown lungs created from living cells.Lung disease in humans, which includes conditions such as emphysema and cystic fibrosis, causes approximately 440,000 deaths per year in the United States alone, according to the Centers for Disease Control and Prevention.

Lung disease is difficult to treat because lung tissue does not sufficiently regenerate, as opposed to skin or muscle cells, which quickly divide to replace damaged areas of tissue. (Niklason speculated that it is not thermodynamically efficient for the body to regenerate the lung’s air sacs.) Therefore, patients with severe lung disease must often undergo risky transplants, for which the 10-year survival rate is 10 to 20 percent.

Niklason said she is hopeful the findings will lay the groundwork for human lung regeneration. Still, she noted that more research into lung tissue decellularization and regeneration would be necessary before the techniques could be applied to human patients. She estimated that any clinical application to human medicine would take at least 20 years to develop.

The study was funded by the Yale School of Medicine Department of Anesthesiology and the National Institutes of Health.

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