Study Gives First Evidence That Adult Human Lungs Can Regrow

Researchers speculate growth was stimulated, at least in part, by stretching caused by exercise

By Barbara Bronson Gray
HealthDay Reporter

WEDNESDAY, July 18 (HealthDay News) -- Researchers have uncovered the first evidence that the adult human lung is capable of growing back -- at least in part -- after being surgically removed.
In an observational study, researchers used MRIs with hyperpolarized helium-3 gas to show that existing alveoli -- the tiny, air-exchange units of the lung -- actually increased in number after a 33-year-old woman had her entire right lung removed due to cancer.

The study showed a 64 percent increase in the number of alveoli in the woman's lung 15 years after surgery. "The research clearly shows that some form of lung growth can occur in the adult human," said study author James Butler, an associate professor of medicine in the department of medicine at Harvard Medical School in Boston.

The new alveoli were all shaped similarly. "It's striking, the degree of homogeneity of the new alveoli, as if the lung was responding to something," Butler added. The cause of the new growth could be stretching of the tissue, perhaps by exercise, he suggested. "Could other bio-molecular growth be triggered by stretch? It's a wide-open question now."

About a year and a half after surgery, the woman began a daily exercise program including walking, cycling and yoga. Previous studies in adult dogs have suggested that lung growth after pneumonectomy (removal of the lung) in dogs was possible, typically after periods of lung stress or strain.
Over a period of 15 years, data measuring lung size and capacity were collected, using common respiratory tests (called FEV and FVC) measuring how much air can be taken in and blown out with deep breaths. In the early months after surgery, the lung responded as researchers would expect. The total lung volume increased and the lung density fell below normal. But, the lung tissue volume gradually started to increase and the density returned to a level normally seen when a deep breath is taken, suggesting the growth of new tissue.


The ability of the lung to regenerate, potentially triggered by exercise, makes sense, said Dr. Norman Edelman, a professor of medicine at Stony Brook University and chief medical officer of the American Lung Association. "When the lung develops in utero [when the fetus is developing], the pulling force of the diaphragm is an important stimulation for the lung to grow," he said. "But, of course, the practical application of the research is a long way off."
Butler said the next step is to do a study involving more people over time. "If we can discover the underlying bio-molecular mechanisms, they would suggest potential therapeutic options," he explained.

 see the original article here

Lung Regeneration Closer to Reality after New Discovery

Researchers from Weill Cornell Medical College say they have taken an important step forward in their quest to "turn on" lung regeneration - a discovery that could lead to treatment for millions of people suffering from respiratory disorders.

In the journal Cell, the research team claims that they have discovered the biochemical signals in mice that initiate the regeneration of new lung alveoli: the tiny, numerous sacs within the lung where oxygen exchange occurs. Specifically, they found that regenerative signals originate from the specialized endothelial cells that line the interior of blood vessels in the lung.

Though it has been long known that mice can regenerate and expand the capacity of one lung if the other is missing, this study now pinpoints the molecular triggers that initiate this process, and the researchers believe these findings hold relevance for humans.

According to lead author, Dr. Shahin Rafii, "Several adult human organs have the potential upon injury to regenerate to a degree, and while we can readily monitor the pathways involved in the regeneration of liver and bone marrow, it is much more cumbersome to study the regeneration of other adult organs, such as the lung and heart.”

For the study, Dr. Bi-Sen Ding, first author of this paper, removed the left lungs of mice and studied the biochemical process of subsequent regeneration of the remaining right lung. Prior research has shown that when the left lung of mice is removed, the right lung regenerates by 80 percent, effectively replacing most of the lost alveoli.

htclick for the complete article on lungs




The researchers found that removal of the left lung triggers receptors on lung endothelial cells that respond to vascular endothelial growth factor and basic fibroblast growth factor. Activating these receptors promotes the creation of another protein known as MMP14. The researchers discovered that MMP14, by releasing epidermal growth factors, sparks the generation of new lung tissue.

The next step for researchers will be to determine in MMP14 and other unrecognized angiocrine factors are responsible for lung regeneration in humans as well as mice. According to Dr. Ding, "We believe the same process goes on in humans, although we have no direct evidence yet.” The study’s authors theorize that patients with COPD have so much damage to their lung endothelial cells that they no longer produce the proper inductive signals, thus impairing lung regeneration.

Co-author of the study, Dr. Zev Rosenwaks theorizes that, “"Perhaps replacement of angiocrine factors, or transplantation of normal lung endothelial cells derived from pluripotent stem cells, could restore lung regeneration. Currently, we are generating pluripotent stem cells derived from patients with genetic pulmonary disorders to identify potential pathways, which may ultimately enhance our understanding of how lung endothelial cells may improve lung function in these patients."