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N.E. researchers create functioning lung tissue

A vital step in the quest to build organs

By Carolyn Y. Johnson
Globe Staff / June 25, 2010

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Two teams of researchers from New England have built living, breathing lung tissue in the laboratory — feats of engineering that could speed up the development of new drugs and bring researchers a step closer to the tantalizing dream of growing replacement lungs for patients.

Both achievements, described in reports published yesterday by Harvard and Yale scientists, are part of broader efforts among researchers to build a range of organs, from the heart to the liver. Such research could provide powerful tools to test drugs and identify toxins, and eventually grow new tissue to repair damaged organs.

Harvard scientists re-created a critical area of lung tissue on a silicon rubber chip the size of a quarter, and found that it responded to bacteria and tiny particles carried in the air just like a living lung. Using a different approach, Yale University researchers regenerated lungs and transplanted them into rats, where they functioned successfully for up to two hours.

This work is not the first successful effort to build functional tissue. In the late 1980s, researchers first began to apply engineering approaches to human tissue, and advances have begun to work their way into the clinic — most notably in advances in artificial skin.

But the two new studies are significant milestones in the quest to build a functional organ in the lab — although it will still be many years yet before doctors reach the science fiction dream of regenerating lungs to help patients.

More immediately, the benefits of the new work could be seen in allowing pharmaceutical companies to test drugs on a tiny, cheap chip that closely resembles the complexity of the human body.

The “lung is pretty tough [to replicate]. It’s also pretty important — people get lung cancer, and lots of people get lung diseases that are pretty serious,’’ said Robert Langer, a professor at MIT who was not involved in either group’s research. Langer said the new techniques also could provide a substitute for animal testing.

For years, scientists have tested drugs using cells in a dish and lab animals. But many organs have layers of complexity that simply can not be replicated with current models, and drugs that show promise in mice often do not pan out as cures in humans.

The lung contains an intricate branching architecture of airways, blood vessels, and hundreds of millions of tiny sacs, called alveoli, where gases are exchanged. And the cells move and are stretched with each breath.

“In an organ, multiple tissues come together at an interface, and synergize. Higher-order structure and physical movements, like the effect of [breathing] movement on a lung, or a heartbeat on the heart’’ need to be considered, said Dr. Donald Ingber, director of the Wyss Institute for Biologically Inspired Engineering at Harvard University and senior author of one of the papers, published in the journal Science.

Ingber and colleagues created tiny, microscopic channels in a clear, silicon rubber chip. Sandwiched in the middle of the channel was a thin, flexible membrane seeded with lung and blood vessel cells that mimicked the wall of the alveoli — the tiny sacs where oxygen enters the bloodstream.

In a living lung, the alveoli stretch and swell as they fill with air, and oxygen enters blood while carbon dioxide exits. Researchers used a vacuum to cause the membrane to stretch.

Then, they tested whether the tiny lung-on-a-chip acted like a lung in the body, seeing how it reacted to bacteria and small particles, such as those found in pollution.

“It has the dynamics of a real lung, with stretching,’’ said Shuichi Takayama, associate professor of biomedical engineering at the University of Michigan, who was not involved in the research. “Testing results seem to really nicely mimic what happens in the body.’’

In a second study published online in the journal Science, Yale researchers took a promising step toward the long-term goal of growing functioning lung tissue for transplant.

First, they removed an adult rat lung and carefully removed all of its living cells. Removing the cells was like taking eggs from an egg carton; it left behind a delicate matrix structure of the lung.

Then, using cells from baby rat lungs, they were able to use that matrix as a scaffold to build a functioning lung that worked in adult rats for up to two hours. Such techniques are at least two decades from being used in people.

“The long-term goal is developing a platform for lung replacement,’’ said Dr. Laura Niklason, a professor of anesthesiology and biomedical engineering at Yale, who led the work. “I’ve seen a lot of lung disease — and lungs don’t get better very well. They don’t heal themselves very well.’’

Boston-area researchers have long played a leading role in the attempt to engineer tissues and organs.

Pioneering efforts by local researchers have included a “biorubber’’ material that could be used to help craft blood vessels, cartilage, and heart tissue, to making a liver-on-a-chip, which could be used to test drugs for toxicity.

At the Wyss Institute, researchers are also crafting a gut-on-a-chip and cancer models. Last year, Harvard researchers announced they had created a pulsing strip of heart muscle from mouse embryonic stem cells.

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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