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Salk lab turns skin cells into human airway tissue

Inder Verma and Amy Firth

Studying diseases that affect the lungs and nearby airways has been limited by the ability to collect diseased tissue from patients and by the complexity of organs. Multiple cell types make up airway tissue, so studying how a disease changes just one cell type in the lab may not be an accurate reflection of the full impact of the disease.

Using reprogrammed skin cells, researchers in the lab of Inder Verma have for the first time used stem cell techniques to grow fully functional assemblies of the cells that line airways leading to the lungs. The lab-grown airway tissue can now be used to study the molecular basis of lung diseases–from rare genetic disorders to common afflictions like asthma and emphysema–and to test new drugs to treat the diseases. The results of the study, a collaboration with Fred Gage, were published in Proceedings of the National Academy of Sciences.

In the new work, the researchers developed the complex airway tissue, composed of four different cell types, by reprogramming skin cells into stem cells, then exposing the stem cells to a unique recipe of chemicals that steered them down a particular airway-specific developmental path. Since skin cells contain the same master set of genes as lung cells, any airway tissue grown from a patient’s skin cells will have the disease-causing gene mutation in them.

“The ability to generate a variety of cells that compose a fully mature lung is the first step to understanding the molecular mechanisms of many lung diseases,” says Verma, who holds the Irwin and Joan Jacobs Chair in Exemplary Life Science and is also an American Cancer Society Professor of Molecular Biology.

While the grown cells aren’t identical to those found in all parts of the lung, similar procedures could pin down how to grow tissue from other sections of the respiratory system. Already the new protocol can be used to develop cell populations to study rare diseases, such as primary ciliary dyskinesia, known to affect the cilia lining airways. In addition, new treatments or genetic therapies could be tested on lab-grown airway tissue derived from an affected patient’s cells.

“It will hopefully become possible one day to correct the genetic mutations in these tissues and engraft them back into the airways of a patient,” says Amy Firth, a postdoctoral researcher in Verma’s lab and first author of the paper (see Next Generation). Airway tissue grown in the lab could also reveal how pollutants or nicotine exacerbate symptoms of diseases not only affected by genetics but by the air a person breathes.