|Lung Stem-Cells and Airway Repair|
The damaged done to our lungs is most often to the alveoli, which makes diffusion difficult and a hallmark of the disease. Stem-cells are repairing the damage in mice during the latest research. The most exciting quote from the article is: "It's too early to say common lung diseases will be treatable, but it's a start, and there's a lot of potential.”
Stem-cell find breathes new life into lung repair
14:12 28 October 2011 by Andy Coghlan
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There is new hope for heavy smokers, people with asthma and those with
chronic lung scarring. Stem cells have been discovered that rapidly rebuild alveoli, the tiny air sacs in lungs – a finding that could herald new treatments for people with damaged lungs. Meanwhile, a signaling molecule that drives regeneration of lung tissue has also been found.
The hitherto unknown stem cells were identified after researchers infected mice with a variant of H1N1 almost identical to the one that caused the Spanish flu pandemic of 1918. Another variant of H1N1 caused the 2009 swine flu pandemic.
Samples taken from the mice showed that straight after infection the virus destroyed over half the original tissue in alveoli – the sacs in lungs vital for absorbing oxygen from inhaled air. Just three months later, however, all the tissue had naturally repaired itself, thanks mainly to the newly discovered stem cells.
"We saw essentially pristine lungs at three months after a loss of 50 per cent of lung tissue," says Frank McKeon of the Genome Institute of Singapore, who led the team.
Multiply and repair
The stem cells multiplied rapidly, creating hundreds of times their original number within a week. Then they migrated to sites of damage where they formed pod-like structures as a prelude to becoming new air sacs.
McKeon's colleague, Wa Xian at the Institute of Medical Biology in Singapore, isolated similar cells from human lung tissue and found that they form the same pod-like structures.
McKeon says that they have probably not been discovered before because the damage caused by the flu virus is more amenable to repair than that caused by bleomycin, a drug usually used to deliberately damage mouse lungs in experiments.
McKeon says the best hope for treating damaged may be through identification of the key signaling molecules that order the cells to rapidly multiply and migrate to sites of damage. With his colleagues, McKeon is now screening potential growth factors in fluid from repair sites in the mouse lungs to work out which do the job. "There are probably 20 to 30 of these factors that we're looking at," he says.
Injecting the right growth factor could aid healing in people with both acute and chronic lung damage. "It's too early to say common lung diseases will be treatable, but it's a start, and there's a lot of potential," says McKeon.
A different group of researchers has managed to identify one such chemical that can drive the regeneration of alveoli – a development also published this week.
"The key is that the blood vessels turn on the pathways for regeneration," says Shahin Rafii of Weill Cornell Medical College in New York City, who led the team. "The cells lining the vessels produce growth factors that trigger it, and the main one is MMP 14, standing for matrix metalloproteinase 14," he says.
Rafii and his colleagues discovered the chemical when they removed one lung from mice, triggering extra alveoli to grow in the other lung. By deliberately blocking the effects of MMP 14, they demonstrated that it was the key factor needed for regeneration – although they did not explore exactly how regeneration occurred.
"The therapeutic potential is tremendous," says Rafii, who is hoping to develop treatments for smoking-related diseases and other illnesses that damage lungs. One option might be to extract cells from the lining of a patient's blood vessels, activate them to produce MMP 14, multiply them and reinject them into the patient.