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Study finds lung stem cells, likely to generate debate

Has potential to lead to ways to fix damage

By Carolyn Y. Johnson
Globe Staff / May 12, 2011

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In a provocative new finding, researchers from Brigham and Women’s Hospital report they have discovered human lung stem cells, which they say can give rise to the many different types of cells in the lung and ultimately may hold the potential to regenerate and repair damaged lung tissue in patients.

The results, published yesterday in the New England Journal of Medicine, challenge the current understanding of how the lung develops and will probably generate significant debate and skepticism within the field. Many scientists did not expect that a single human lung stem cell would give rise to all the many cell types found in the lung.

“Elements of the extensive experiments reported here are sure to be controversial, and some may even prove to be incorrect,’’ Dr. Harold Chapman — a professor in the division of pulmonary and critical care medicine at the University of California, San Francisco — wrote in an editorial accompanying the paper. “But the essential finding . . . is convincing.’’

Starting with human lungs from a tissue bank, the scientists identified lung stem cells by looking for particular markers. Then they did tests to demonstrate those cells had the essential qualities of stem cells: they could make copies of themselves and also give rise to many different types of cells in the lung. They inserted the human cells into injured mouse lungs and found that the cells replaced the injured tissue, generating multiple types of cells that grew into the intricate structure of lungs.

In the lung, “there are several cells which have been claimed to possess the properties of stem cells, but don’t have the biological characteristics,’’ said Dr. Piero Anversa, a professor of medicine at the Brigham and coauthor of the study. “What we have found is . . . rather unexpected and seems to be, at least in the initial study, powerful.’’

Dr. Joseph Loscalzo, chair of the Brigham department of medicine and also a coauthor of the study, said the team had not yet been able to determine whether the new tissue in the mouse lungs was functional.

The next step, he said, was to try the approach in animals whose lungs have been injured in ways similar to the damage that occurs in human lung diseases.

Scientists not involved in the work said the study was important but that it would be essential for the experiment to be repeated.

The paper is “addressing an important problem; it’s daring in its conclusions,’’ said Dr. Kenneth Chien, a stem cell biologist at Massachusetts General Hospital and the Harvard Stem Cell Institute. “At the same time, the technology being used has its own inherent limitations, which may make it difficult to draw firm conclusions and has led to difficulties in others easily replicating the work of the group.’’

Anversa’s work has fired vigorous debate among stem cell scientists before. A paper from his lab in 2001 found that bone marrow stem cells could transdifferentiate, giving rise to cells that could repair the heart. That work has been controversial, with some scientists disputing the validity of the findings.

The editorial noted that the find has tremendous potential but also that there are many unanswered questions.

“If this is true, the identification of these stem cells promises to overcome one of the major hurdles in human lung generation,’’ Chapman wrote. “In spite of the many major uncertainties that presage translation of the current results into applications in the clinical arena, these new findings should energize the field.’’

Several scientists said one way to follow up the study would be to use genetic markers to trace whether that particular stem cell gives rise to the other cells.

For example, Carla Kim, an assistant professor at Children’s Hospital Boston who focuses on lung stem cells, said that after finding a stem cell in the mouse lung that her group thinks gives rise to epithelial cells that line the airways and air spaces, her group has been using genetic markers to unequivocally demonstrate that the stem cells were the source of the new cells.

Doing that type of genetic tracing method could help answer some of the questions that will be generated by the new finding.

The new paper will, scientists predicted, generate new interest in the field and spur further research.

“I think it’s a remarkable paper in many ways; it opens up a whole field,’’ said Dr. Alan Fine, a professor and lung biologist at Boston University School of Medicine. “I think the field will be advanced once some of these studies can be done in mice and be reproduced.’’

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

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