Origin of lung mucus glands found, insights for cystic fibrosis, asthma

Last week's big news at CIRM was the election of Jonathan Thomas as the new governing board chair, as we announced late Wednesday night. He will be replacing Robert Klein, who has served the agency since its inception in 2004. Not that anyone can replace Klein, exactly, but Thomas seems eager to step in and start leading the agency.

While many of us at CIRM were distracted by our board meeting and subsequent leadership change, CIRM grantees kept on doing science, as evidenced by a paper in Stem Cells which came out today.

Scientists with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have fund the stem cell that makes all the cells of the mucus glands in the airways of the lungs. By and large, scientists assume that most tissues of the body arise from a pool of tissue-specific stem cells. These stem cells have been identified in the blood system, brain, muscle, skin and a variety of other tissues. Once found, scientists can begin developing ways of harnessing those cells to treat disease.

Until assistant professor Brigitte Gomperts and postdoctoral scholar Ahmed Hegab published this work, nobody knew the origin of the mucus cells in the airway. These cells play a critical role in protecting the body from infectious agents or toxins in the environment. A UCLA press release quotes Gomperts:

“We’re very excited that we found this population of cells because it will allow us to study mechanisms of diseases of the upper airway. For example, there currently are no treatments for excess mucus production, which we see in cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). But if we can understand the mechanisms of how these stem cells repair the mucus glands, then we may be able to find a way to put the brakes on the system and prevent mucus over production.”

I often read about people who claim that adult stem cells are as effective at treating disease as embryonic stem cells. What people seem not to understand is that there is no one adult stem cell. Stem cells of the blood system are fantastic, but they don't repair muscle, skin, brain, or, in this case, mucus glands. Finding these tissue-specific stem cells is the necessary first step to to developing new therapies based on these cells.

Stem Cells, June 27, 2011
CIRM Funding: Brigitte Gomperts (RN2-00904-1)

A.A.

Lung stem cell found, controversy ensues

Scientists at Brigham and Women's Hospital in Boston have reported that they identified a stem cell in lung. The work was published in the May 12 issue of the New England Journal of Medicine.

In the popular press you often read that adult stem cells exist in all the tissues of the body. This is likely true, but the reality is that scientists have only identified stem cells in a handful of tissues. They think all or most tissues contain a reservoir of restorative stem cells, but can't necessarily put their finger on them. And cells you can't identify are cells you can't turn into therapies or use to study disease.

Now that the team has isolated these potential lung stem cells, they can start thinking about using them. An Associated Press story quotes the study's authors Piero Anversa and Joseph Loscalzo:

Loscalzo said it's too early to tell what lung diseases might be treated someday by using the cells. He said researchers are initially looking at emphysema and high blood pressure in the arteries of the lungs, called pulmonary hypertension. Emphysema is a progressive disease that destroys key parts of the lung, leaving large cavities that interfere with the lung's function.

Anversa said the cells may also prove useful to build up lungs after lung cancer surgery. It's not clear whether they could be used in treating asthma, he said.

While a lung stem cell theoretically could be used to grow a lung in a lab for transplant, Loscalzo said that would be very difficult because the lung is so complex. Instead, he said, scientists will first look at isolating the cells from a patient, multiplying them in the laboratory, and then injecting them back into the patient's lung.

Nature has a blog entry on this paper in which they point out that Anversa has made controversial claims about stem cells in the past, including a 2001 paper in which he claimed bone marrow stem cells could turn into heart muscle in mice, work that Stanford's Irv Weissman said he couldn't replicate.

Nature quotes Amy Wagers, one-time post-doctoral researcher with Weissman and now scientific neighbor of Anversa's. Wagers works at the Joslin Diabetes Center, also affiliated with Harvard:

When I began my position as a postdoctoral fellow in Irv Weissman's lab at Stanford, there was a lot of enthusiasm surrounding the idea that hematopoietic stem cells in the bone marrow might spontaneously transdifferentiate to produce non-blood tissues. I rigorously tested this idea and found such activity to be negligible, if present at all. That changed the course of investigation by shifting the emphasis towards defining endogenous tissue progenitor cells that carry out regenerative functions.

All this just goes to show that grand pronouncements (or perhaps just simplified pronouncements) in the press don't always tell the full story about the science. Time will tell whether the lung stem cells announce today will turn out to be therapeutically useful, and in what way.

A.A.