An engineered lung worked when implanted into a rat

An engineered lung worked when implanted into a rat.

Ker Than for National Geographic News Published June 2010

For the first time scientists have reconstructed working lungs in the lab and transplanted them into a living animal.

The achievement is a breakthrough in biomedical engineering that could lead to replacement lungs for humans in the near future, experts say.

Currently, the only way to replace diseased lungs in adults is a lung transplant, a high-risk procedure that's vulnerable to tissue rejection.

In a new study, researchers took lungs from a living rat and used detergents to remove lung cells and blood vessels, revealing the organ's underlying matrix.

This lung "skeleton"—made of flexible proteins, sugars, and other chemicals—consists of a branching network that divides more than 20 times into smaller and smaller structures. (See an interactive graphic of lung structure.)

The researchers placed these "decellularized" lungs into a bioreactor, a machine filled with a slurry containing different types of lung cells extracted from rat fetuses.

(Related: "Scientists Grow Lung Cells From Stem Cells.")

Within several days, the fetal cells naturally attached to the lung matrix and formed a functional lung.

"By and large, the correct subsets of cells went to their correct anatomical locations," explained study leader Laura Niklason, a biomedical engineer at Yale University. "It appears that the lung matrix has cues, or 'zip codes,' that tell the cells where to land."

When the team implanted the engineered lungs into an adult rat for short periods of time—between 45 minutes and two hours—the lungs exchanged oxygen and carbon dioxide in the same way as natural lungs.

"Leap Forward"
By using a natural lung matrix, Niklason's team has avoided one of the biggest hurdles of lung-regeneration attempts—finding a suitable "scaffold" for lung cells to attach to.

Because manufacturing techniques cannot yet replicate nature's complex design, attempts to create synthetic scaffolds have been unsuccessful.

Niklason spent several years trying to create a synthetic lung scaffold, but in the end concluded it was too difficult.

"I decided I couldn't do it, and probably nobody else could either," she said.

The new research represents a "real leap forward" in lung regeneration, said Peter Lelkes, a biomedical engineer at Drexel University in Philadelphia.

"People have engineered organs such as bone and cartilage before, but by comparison to the lung, these are all kids' games," added Lelkes, who was not involved with the study.

Stem Cell Hurdle
Niklason estimates it will be about 20 to 25 years before her team's technique can be used in humans.
That's because a few technical and scientific challenges remain.

Chief among these is finding ways of creating stem cells—which can transform into any other type of cell—from patients with lung disease. No techniques currently exist for creating such cells, which would carry no risk of immune rejection.

(Related: "Liposuction Fat Turned Into Stem Cells, Study Says.")

"The stem cell issue," Niklason said, "is really the big fundamental scientific hurdle."

The research is detailed in this week's issue of the journal Science.

Image courtesy Science/AAAS

Scientists create replacement lungs

Scientists create replacement lungs
US scientists have reported important progress towards building new human lungs by successfully implanting lab-cultivated cells into a rat's lungs, and by creating an artificial device on a microchip that mimics the human lung.

Yale University researchers managed to create lungs that worked from 45 to 120 minutes by using laboratory-cultivated cells and implanted them into rats, a scientific first.

Separately, researchers with the Wyss Institute at Harvard University, Harvard Medical School and Children's Hospital Boston created a device that acts like a human lung using blood vessel cells. It is about the size of a rubber eraser.

The artificial lung can be used to test the effects of new medicine and toxins on human lungs, said Wyss Institute director Donald Ingber and the study's main author.
The mini lung-on-a-chip "merges a number of technologies in an innovative way," said MIT Institute professor Robert Langer on Thursday.

"I think it should be useful in testing the safety of different substances on the lung and I can also imagine other related applications, such as in research into how the lung functions," he added.
Both research studies appear in the June 25 edition of the journal Science.
For the first study, researchers took adult rat lungs and removed their existing cellular components.
They preserved the matrix and branching structures of the airways and vascular system, which they later used to grow new lung cells.

"When implanted into rats for short intervals of time (45-120 minutes), the engineered lungs exchanged oxygen and carbon dioxide similarly to natural lungs," the researchers said.

"We succeeded in engineering an implantable lung in our rat model that could efficiently exchange oxygen and carbon dioxide, and could oxygenate hemoglobin in the blood," said lead author Laura Niklason from Yale University.

"This is an early step in the regeneration of entire lungs for larger animals and, eventually, for humans," she said.

Niklason however warned that it will take years of research with adult stem cells to see if lungs can be regenerated in vitro, successfully implanted into patients, and made sure they function properly.


The Yale team found that the engineered lungs were similar to those of native tissues, and properly exchanged oxygen and carbon dioxide when implanted.

Some 400,000 people die annually in the United States of lung diseases.

Lung tissue is especially difficult to regenerate because it rarely repairs beyond the microscopic level, researchers said. "The only current way to replace damaged adult lung tissue is to perform lung transplantation, which is highly susceptible to organ rejection and infection and achieves only 10 per cent to 20 per cent survival at 10 years," the Yale researchers said.

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