Artificial Lung "Breathes" in Rats: Study

Reuters: WASHINGTON

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U.S. researchers have created a primitive artificial lung that rats used to breathe for several hours and said on Tuesday it may be a step in the development of new organs grown from a patient's own cells.

The finding, reported in the journal Nature Medicine, is the second in a month from researchers seeking ways to regenerate lungs from ordinary cells.

In the latest study, Harald Ott and colleagues at Massachusetts General Hospital and Harvard Medical School in Boston removed the cells from rat lungs to leave a scaffolding or matrix.

They soaked these in a bioreactor along with several types of human lung cells, creating pressures to simulate the pressure inside a body to make the lung workable and flexible.

The cells took up residence and grew into different tissue types seen in a lung, Ott's team reported.

When transplanted into rats, they worked for about six hours, although imperfectly.

The researchers said it may be possible to try the experiment with more immature stem cells, the body's master cells. These could include embryonic stem cells, which can mature into any cell type in the body, or induced pluripotent stem cells -- ordinary cells with genes added to make them behave like flexible stem cells.

The potential market is large and dozens of companies are launching into regenerative medicine, as are academic labs like those at Harvard.

"Nearly 25 million people live with chronic obstructive pulmonary disease and approximately 120,000 patients die from end-stage lung disease annually in the United States alone," Ott's team wrote.

"Lung transplantation remains the only definitive treatment for end-stage lung disease. As with other organs, however, the supply of donor lungs is limited. In 2005, only one out of four patients waiting for a lung underwent transplantation," they added, citing the United Network of Organ Sharing.

Last month, a team at Yale University in Connecticut implanted engineered lung tissue into rats that helped the animals breathe for two hours.

(Editing by Todd Eastham)

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Rat Lungs Renovated in Lab

The new technique that uses stem cells to build better lungs could eventually help save lives.

By Eric Bland

From: http://news.discovery.com/

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Although the new research is promising, more study is needed before the reseeding technique could be applied to human patients. Click to enlarge this image.
Hemera

"Reseeding" lungs with a patient's own stem cells before a transplant could save millions of lives.

Scientists from Yale University have developed a technique to remove all cells from a lung and then reseed the remaining connective tissue scaffold with a patient's own cells. The technique could be used with lung transplant patients.

"This is really the first paper that talks about engineering an entire lung that can be implanted and can exchange gas," said Laura Niklason, a scientist at Yale University and a co-author on the Science paper. "Previous work was scaled down... a far cry from engineering an entire tissue that a surgeon could pick up."

For now, the Yale scientists are only sewing reseeded lungs into rats, not humans.

Lung transplants are risky procedures. Given complications, organ rejection and other problems, the survival rate after 10 years is between 10 and 20 percent. But if a patient's own stem cells re-colonized the lung, the chance of organ rejection would drop dramatically, which should raise the long-term survival rate.

The first step toward saving human lives is by sacrificing a few rats. The scientists first removed four left lungs from four rats. Next, they bathed the lungs in a solution to destroy and then flush out all the living organic matter. Only a scaffold of connective tissue remained.

Next, the scientists injected lung stem cells into the trachea, and a slurry of lung vascular tissue into the artery leading into the lungs. One week later, the vascular and lung cells had re-colonized the connective tissue.

After removing the left lungs from a new set of rats, the Yale scientists implanted the reseeded lungs and compared them to their untouched counterparts. The reseeded lungs exchanged oxygen and carbon dioxide as well as the rats' original lungs.

The experiment was a success, but patients shouldn't start lining up at doctors offices just yet. After several hours, blood clots formed in the reseeded lungs, which would eventually kill a rat or person.

Niklason thinks this occurred because the lungs weren't fully reseeded. If the cells had been given more time, they would have successfully covered all surfaces inside the lung, and clotting would have been avoided.

Even so, there are other significant hurdles that must be overcome before human lungs can be grown. Niklason estimates it will take at least two decades for stem cell researchers to catch up with the best cells to reseed human lungs and, should that prove successful, to perform the necessary clinical trials.

Daniel Weiss, a scientist at the University of Vermont not involved in the research, agrees that at least 10 or 15 years and "a lot of work" remains before the lung reseeding technique could be used in humans. Nevertheless, Weiss is very excited by the new research.

"We are looking at millions of people worldwide dying because there is no cure (for diseases like emphysema and lung cancer)," said Weiss. "We desperately need a cure, and this gives us a lot of hope."

Lungs aren't the only organs that could be reseeded, said Weiss. Kidneys, liver, hearts and other organs could all potentially be reseeded with a patient's own cells, which are grown and then implanted into the patient to eliminate organ rejection.

"No one expected this to work so well, not even for a short amount of time," said Weiss. "This research will set the stage for years to come."

Marijuana Cuts Lung Cancer Tumor Growth In Half, Study Shows

The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.

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They say this is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.

THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer.

"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.

Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.

In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.

Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.

Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.

Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.

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Adapted from materials provided by American Association for Cancer Research.