The discovery that human lung stem cells do exist, contrary to much current scientific thinking, is likely to lead to completely new treatments that repair and regenerate damaged tissue in patients with chronic lung diseases, but not for some time because there is still a lot of work to be done, said the authors of a paper published online this week in the New England Journal of Medicine.
Corresponding author Dr Piero Anversa, director of the Center for Regenerative Medicine at Brigham and Women’s Hospital (BWH) in Boston, Massachusetts, and colleagues, found that the human lung stem cell is self-renewing, plays an important role in regenerating tissue and and may also help repair damaged lung cells.
They also found that the stem cell can form and integrate various biological structures of the lung, including alveoli, the tiny breathing sacs where oxygen and carbon dioxide are exchanged between air and blood; bronchioles, the small airways that connect the alveoli to the main airways; and pulmonary vessels, the blood vessels that serve the lungs.
Anversa told the media that they have for the first time found and described a “true human lung stem cell”.
“The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung,” he added.
Co-author Dr Joseph Loscalzo, chair of the Department of Medicine at BWH said they were “excited about the impact this discovery could have on our ability to regenerate or recreate new lung tissues to replace damaged areas of the lungs”.
However, he said more research is now needed to build on these “critical first steps” before work can start on developing new clinical treatments for people with currently untreatable lung diseases.
In their paper the researchers describe how they isolated the the human lung stem cell from lung tissue taken from surgical samples and, working with cultures and laboratory mice, they then tested what they were capable of doing.
In culture (“in vitro”), they showed that the stem cell could divide into new stem cells and also into cells that would turn into various types of lung tissue.
And then, after injecting the stem cells into mice with damaged lungs (“in vivo”), they found they differentiated and formed various biological structures in the lungs, including new bronchioles, alveoli and pulmonary vessel cells. Not only did they make the new structures but they also wove them into the mice’s existing lung tissue.
In a final stage of the study, the researchers took tissue from the treated mice, isolated stem cells from it, and then used them in new mice with the same results.
Thus they were able to show that that the cell they discovered was a “true stem cell” because it met all three criteria for categorizing a stem cell: it is self-renewing, it forms many types of lung cell, and, with the last part of the experiment, it is transmissible.
The discovery is a challenge to current scientific thinking about lung cells, says Dr Harold A. Chapman, from the University of California, San Francisco, in an accompanying editorial. Until this study, scientists thought there were no cells in the lung that could differentiate into the various types of lung cell.
Chapman, an expert in pulmonary and critical care medicine, writes that parts of the “extensive experiments” that the researchers report may even prove to be wrong, but overall, the findings are “convincing”.
A grant from the National Institutes of Health helped pay for the study.
“Evidence for Human Lung Stem Cells.”
Jan Kajstura, Marcello Rota, Sean R. Hall, Toru Hosoda, Domenico D’Amario, Fumihiro Sanada, Hanqiao Zheng, Barbara Ogórek, Carlos Rondon-Clavo, João Ferreira-Martins, Alex Matsuda, Christian Arranto, Polina Goichberg, Giovanna Giordano, Kathleen J. Haley, Silvana Bardelli, Hussein Rayatzadeh, Xiaoli Liu, Federico Quaini, Ronglih Liao, Annarosa Leri, Mark A. Perrella, Joseph Loscalzo, and Piero Anversa.
New England Journal of Medicine, 2011; 364 (19): 1795-1806
DOI: 10.1056/NEJMoa1101324; published online 12 May 2011.
Additional source: Brigham and Women’s Hospital.
Written by: Catharine Paddock, PhD