Fibrosis is a process in which scar tissue forms in internal organs as the body attempts to repair damage—an attempt that ultimately fails. In pulmonary fibrosis, this damage can be caused by factors such as smoking, air pollution, exposure to harmful chemicals, viral infections such as COVID-19 or genetic predispositions.
All these factors can harm healthy lung tissue, which is replaced by connective tissue rich in collagen, primarily made up of fibroblasts. This replacement tissue prevents the lungs from performing their normal functions — absorbing oxygen and releasing carbon dioxide — and significantly impairs lung function. Collagen also makes the tissue stiffer and less flexible, reducing its mobility.
Symptoms of pulmonary fibrosis include difficulty breathing, dry cough, fatigue, reduced ability to perform physical exertion, increased heart rate, wheezing, and a drop in blood oxygen levels, which can deteriorate to the point of requiring a ventilator or even a lung transplant.
If the damage originates from a viral infection, the disease can develop very quickly, though it is more commonly a chronic condition that develops over years. Currently, there is no cure for pulmonary fibrosis, although its progression can sometimes be slowed. In a recent study, researchers have succeeded in improving the condition of mice with pulmonary fibrosis.
The lungs consist of a network of tubes called bronchi and clusters of tiny sacs called alveoli. Gas exchange, when oxygen is absorbed and carbon dioxide is released, occurs in the alveoli. The lungs also contain lung stem cells (progenitor cells), which differentiate into the cells that form the alveoli and bronchial walls, enabling the regeneration of lung tissue. In cases of pulmonary fibrosis, these stem cells are damaged, leading to cumulative impairment of lung function.
Mice with pulmonary fibrosis
In the research group led by Yair Reisner at the MD Anderson Cancer Center in Texas, US, lung stem cells were successfully transplanted into mice with lung damage caused by naphthalene exposure, following radiation-induced damage to the mice's original lung stem cells. In the new study, the researchers attempted to transplant lung stem cells into the lungs of mice suffering from pulmonary fibrosis.
The mice used in the experiment underwent treatments designed to simulate the conditions of pulmonary fibrosis patients in two different ways. In the first experiment, the mice were treated with a chemotherapeutic drug for four weeks, causing pulmonary fibrosis to develop.
By the end of these four weeks, drug treatment was discontinued, lung stem cells harvested from the lungs of healthy mice were transplanted into the lungs of the drug-treated mice. The transplanted stem cells were marked with a red protein, making them easily identifiable in the mice that underwent transplantation.
The transplanted stem cells integrated easily into the lungs, without the need for radiation to destroy the original cells, as was required in earlier studies. Eight weeks after transplantation, the transplanted stem cells had successfully differentiated into the desired types of lung cells and had formed new alveoli. The lungs of transplanted mice exhibited significantly less scarring, with lung function reaching 75% of the levels observed in healthy mice. In contrast, mice treated only with the chemotherapeutic drug, without stem cell transplantation, retained just 40% of normal lung function.
In the second experiment, the researchers worked with genetically engineered mice carrying a mutation that disrupts the mechanism protecting telomeres—the ends of chromosomes. The mutation was designed to become activated only after the mice were given the anti-cancer drug tamoxifen, causing them to spontaneously develop fibrosis within two to three months.
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In these mice, the transplanted stem cells also integrated into the lungs, differentiated to form new alveoli, reduced scarring and restored lung function to levels comparable to those of healthy mice.
Currently, lung stem cells, such as those used in this study, can be obtained solely from organ donation. However, researchers hope that in the future, it will be possible to grow stem cell cultures from healthy donors for transplantation in the laboratory. If this becomes feasible, it could represent a significant advancement in the treatment of pulmonary fibrosis.