Deep breath

Lung diseases, such as emphysema, bronchitis, asthma, and cystic fibrosis are the second leading cause of death in the world. In the United States alone there are more than 35 million Americans suffering from chronic lung diseases. It is possible that the scientists of the Weizmann Institute of Science have now found an initial direction that may, perhaps, in the future, lead to the development of measures to relieve those suffering from these diseases, and to repair lung tissue. Their findings, recently published in the scientific journal Nature Medicine, show how it might be possible to harness embryonic stem cells for the repair.

The research - carried out as part of the doctoral thesis of Dr. Chava Rosen, from Prof. Yair Reisner's research group in the Department of Immunology of the Weizmann Institute of Science - began due to the great similarity between the stem cells residing in the lungs and the stem cells of the bone marrow. In both, the stem cells are not evenly distributed, but are concentrated in designated niches, where all the factors these cells need to thrive are present. "That's why," says Prof. Reisner, "we wanted to know if it is possible to use the knowledge and laws we know from bone marrow transplantation, and apply them to lung healing."

A bone marrow transplant is based on two main factors: the ability of the blood stem cells, after being introduced into the bloodstream, to independently navigate their way to the niches, and then make room, in the niches themselves, for the transplanted stem cells. Prof. Reisner and the members of his group wanted to check whether this method could also be used in lung stem cell transplantation. But before that they had to find a source of lung stem cells that could be used in a transplant, since lung tissue is a rather rare "commodity".

Comparison between the state of the lung after six weeks from the date of stem cell transplantation (right), and its development after 16 weeks (left). In green: cells derived from the transplanted stem cells against the background of the transplanted lung cells, which are not green. The images show the continuous formation of new lung cells, replacing the damaged cells. Photography using a 2-photon microscope
Comparison between the state of the lung after six weeks from the date of stem cell transplantation (right), and its development after 16 weeks (left). In green: cells derived from the transplanted stem cells against the background of the transplanted lung cells, which are not green. The eight… see more

The institute's scientists overcame these obstacles by using 20-week-old embryonic stem cells, after they were able to determine that this is the ideal length of time to use the cells (younger cells will not complete the differentiation process, while older cells may become cancerous cells). To make room in the alcoves, the scientists developed a unique method that made it possible to prepare them for the arrival of the transplanted cells, and thus were able to perform a series of experiments in which, with the help of a simple injection into a vein, they injected the stem cells into mouse models with damaged lungs. The stem cells of the embryonic lungs navigated their way, were absorbed into the lungs, and after about six weeks they differentiated as normal lung cells. The result was a complete restoration of the mice's lungs, with a significant improvement in breathing.

In the future, Prof. Reisner hopes to determine what is the minimum dose of drugs that help prevent transplant rejection, which will allow the stem cells to be transplanted into the lungs of people who need it. "But the real vision based on these successes," says Prof. Reisner, "is a lung tissue bank, which can be used as a source of embryonic stem cells." Through such a bank, we may be able to create available and effective treatment for those suffering from lung diseases.