One Type of Lung Cell Can Regenerate Another

A collaboration between the Perelman School of Medicine at the University of Pennsylvania and Duke University has found that lung tissue has a much great ability to regenerate than previously thought.

Lungs contain thousands of tiny clusters of sacs called alveoli. Gas-exchange between the air and our blood stream occurs across the thin lining of the alveoli, which are lined with extensive networks for diminutive blood vessels called capillaries. The cells that form the paper-thin lining of the alveoli are called type 1 cells. Within the alveoli are cells called type 2 cells, which secrete surfactant; a soapy substance that prevents the alveoli from collapsing upon themselves when we exhale. Some premature babies do not make enough surfactant and must be treated with surfactant to help them breathe.

Work in mice demonstrated that both type 1 and type 2 cells descend from a common embryonic precursor during lung development. When mice had bits of their lungs removed, labeling studies established that the newly re-established type 2 cells were made from type 1 cells and that some of the newly made type 1 cells were formed from type 2 cells. These results were confirmed by cell culture experiments that grew single type 1 or type 2 lung cells in culture; in both cases, the cultures gave rise to mixed cultures consisting of both type 1 and type 2 lung cells. These data demonstrate that type 1 lung cells can give rise to type 2 lung cells and visa versa.

Previously, the Duke University term had demonstrated that type 2 lung cells in mice not only produce surfactant, but also function as progenitors for other lung cells in adult mice. This shows that type 2 lung cells can definitely differentiate into type 1 lung cells. However, there was no evidence that type 1 lung cells could give rise to other types of lung cells.

In this present work, however, lung injury in mice stimulated the type 1 cells to divide and differentiate into type 2 cells over a period of three weeks while the lung regenerated. According to Jonathan Epstein from the University of Pennsylvania, It’s as if the lung cells can regenerate from one another as needed to repair missing tissue, suggesting that there is much more flexibility in the system than we have previously appreciated. These aren’t classic stem cells that we see regenerating the lung. They are mature lung cells that awaken in response to injury. We want to learn how the lung regenerates so that we can stimulate this process in situations where it is insufficient, such as in patients with COPD (chronic obstructive pulmonary disease).”

This is one of the first studies to demonstrate that mature cells that were thought to be completely at the end of their growth and differentiation capabilities can revert to an earlier state under the right conditions without the use of transcription factors, but by responding to damage.

These two research teams are also applying the approaches outlined in this publication to cells from other tissues, such as the intestine and skin, in order to study the mechanisms of cell maintenance and differentiation, and then relate these same mechanisms back to the heart. They also hope to apply these findings in clinical settings for patients who suffer from idiopathic pulmonary fibrosis, acute respiratory distress syndrome and other such conditions where the alveoli cannot supply sufficient amounts of oxygen to the blood.