Stem Cells Repair Lung Damage After Flu Infection

Everyone has struggled with influenza at some point in their lives. This seasonal infection can knock us for a loop and decrease our lung capacity for an inconvenient period of time. How does our body cope with it? In the first place our immune response destroys the influenza virus and the cells infected with it. Secondly, the lung regenerates damaged cells to reclaim the lost lung capacity. Researchers have recently identified and characterized the adult stem cells that can regenerate lung tissue. These findings come from studies of isolated human stem cells, and from parallel studies of mice infected with a particularly nasty strain of H1N1 influenza virus. These findings could potentially be the impetus for new regenerative therapies for acute and chronic airway diseases.

The main authors of this work Frank McKeon of the Genome Institute of Singapore and the Harvard Medical School in Boston, and Wa Xian of the Institute of Medical Biology in Singapore and the Brigham and Women’s Hospital in Boston published this research in the October 28th issue of the prestigious journal Cell.

The H1N1 strain of the influenza virus is as close as you can get to the virus that was responsible for the 1918 influenza pandemic. H1N1 can cause massive lung damage with lots of inflammation and loss of lung tissue. Such infections produce acute respiratory distress syndrome, marked by extensive lung damage and low levels of oxygen in the blood. What hasn’t been clear is what happens to the lungs of those who manage to survive, since two months after the infection, the lungs look normal again in those who survived the infection.

In this paper, studies in influenza-infected mice showed that lungs are capable of true regeneration. Stem cells found along the surfaces of the airways (in the bronchiolar epithelium) proliferate rapidly in mice after viral infection and migrate to sites of damage. Once the stem cells reach the sites of lung damage, they assemble into stem cell “pods” and activate genes that identify them as lung alveoli, which are the small, hollow structures that function as the sites of gas exchange in the lung.

McKeon and Xian were able to clone these same stem cells from human lung tissue. Even if grown in a laboratory culture dish, these lung-specific stem cells show that they can form alveolar-like structures. This is in spite of the fact that these stem cells from the bronchiolar epithelium have a gene expression profile that is very similar to stem cells found in the upper respiratory airways.

This work suggests that airway stem cells are an important and underappreciated ingredient in regenerative medicine. However, in the case of severe, fast-moving infections, the damage to the lungs would overwhelm the regenerative capacity of the lungs. McKeon noted: “The problem in the case of a pandemic is that people die quickly. It is hard to imagine how a cell-based treatment will play in [sic] those time constraints.”

While McKeon is certainly correct, such stem cell-based therapies or secreted factors identified by this study could play an important role in therapies that attempt to enhance the speed of lung regeneration. Such regenerative therapies could aid in those with hard-to-treat condition like pulmonary fibrosis, in which lung tissue becomes scarred. “Pulmonary fibrosis is a bad disease,” McKeon said. “The question is: could you get rid of the fibrosis and replace it with real lung tissue?”

A second study published in the same issue of Cell identifies those molecular pathways in the lung that may also lead to new strategies for encouraging lung regeneration. In that case, researchers led by Shahin Rafii at Weill Cornell Medical College examined mice with one lung removed, a treatment that causes the remaining lung to produce more alveoli.