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Rats Breathe With Lab-Grown Lungs

24 June 2010 2:53 pm
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Petersen et al., Science

Lung "skeleton." The underlying air passages (left) and blood vessels (right) remain after lungs are decellularized.

For the first time, an animal has drawn a breath with lungs cultivated in the lab. Although preliminary, the results might eventually lead to replacement lungs for patients.

People whose lungs are failing because of diseases such as emphysema or cystic fibrosis face a grim outlook. Only 10% to 20% of patients who undergo lung transplants survive for 10 years, versus about 50% for heart recipients. Research to create new lungs in the lab has lagged because of their complex structure and multiple cell types, notes biomedical engineer Laura Niklason of Yale University.

Tissue engineers are enthusiastic about a technique called decellularization that involves using detergent to remove all of the cells from an organ, leaving a scaffold consisting of the fibrous material between cells. The material serves as a template for fresh cells, orchestrating their assembly and growth into a new organ. The technique has yielded implantable liver grafts for rats. And in 2008, a 30-year-old woman received a replacement for one of the lung's main air passages, which scientists had seeded with her own cells.

Now Niklason and colleagues say they have used the method to produce rodent lungs. The team started with decellularized adult rat lungs, which retain the organs' branching airways and blood vessel network, and added a mixture of lung cells from newborn rats. Niklason says that the crucial step was nurturing the would-be lungs in a bioreactor that circulates fluid—simulating what would happen during fetal development—or air through them. The cells stuck to the scaffold in the right locations and multiplied. After up to 8 days in the bioreactor, they had coalesced into what the researchers' tests indicated was functional lung tissue.

artificial lung

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To make a lung. This video shows the procedure the researchers followed to grow lungs in the lab and implant them into rats.
Credit: Video file courtesy of Laura Niklason and Thomas Petersen

To determine whether the new organs worked, the researchers removed rats' left lungs and stitched in lab-grown replacements. X-rays showed that the implanted lungs were inflating, though not fully. Tests of gas levels in blood flowing to and from the replacement organs showed that they were taking in oxygen and releasing carbon dioxide at 95% of normal efficiency. The researchers allowed the animals to breathe with the lungs for up to 2 hours before euthanizing them because of blood clots.

"We've shown that it's possible to engineer a lung that can perform the single most important function—exchange of gases," says Niklason, whose team reports its findings online today in Science. She describes the results as one advance in a "20- to 25-year project" and cautions that a huge obstacle lies ahead. Researchers need to identify cells—possibly adult stem cells from the patient—that can reconstruct lung tissue without provoking attack by the immune system, the problem that plagues current transplant recipients.

Tissue engineer Joan Nichols of the University of Texas Medical Branch in Galveston praises most of the study. "It started out beautifully, it was so well done." However, she argues that the organs were implanted prematurely. The bleeding the researchers detected within the lungs suggests that the organs weren't ready, she says. Nichols recommends a much longer growth period—say, 60 days—and further testing to make sure the lungs are sound. "The answer is not just to implant and see if it works," she says.