The lungs are also recovering
Researchers at Harvard University and the Singapore Genome Institute, working under the leadership of Professor Frank McKeon, cultured stem cells capable of giving rise to full-fledged functional lung alveoli.
For many years, clinicians have observed that patients who have suffered acute respiratory failure syndrome, in which extensive regions of lung tissue are destroyed, often recover a significant part of the damage within 6-12 months. However, the mechanisms of this phenomenon have remained a mystery until now.
To test the ability of lung tissue to recover, the researchers infected mice with a sublethal dose of a dangerous strain of H1N1 influenza A virus, similar to the strain that caused the epidemic of the so-called "swine flu" among humans. 2 months after infection, the virus destroyed almost 60% of the lung tissue of animals, but after 3 months, the results of histological analysis indicated a complete restoration of the respiratory organs.
Areas of destroyed lung tissue are outlined with pink dye:
on the left – immediately after a severe viral lesion, on the right – in the process of regeneration.
Histological analysis also showed that lung tissue damage triggers the active proliferation of special bronchial epithelial cells characterized by p63 protein expression, which subsequently migrate to the damaged areas and give rise to new alveoli.
Using methods of cultivation of epidermal skin cells adapted to the needs of lung epithelial cells, researchers have grown three types of stem cells isolated from the human respiratory tract in laboratory conditions. Cells of one of the types, like cells that provide the restoration of the lungs of mice, differentiated and formed structures consisting of cells whose genetic profile corresponded to the genetic profile of the alveoli. Biochemical analysis of these structures revealed a whole complex of molecules known for their ability to control the behavior of cells.
Researchers are currently exploring the possibility of using these factors secreted by cells forming new alveoli to treat asthma and chronic obstructive pulmonary disease (COPD), often the result of long-term smoking.
As part of a parallel work, Cornell University scientists were able to identify one of these biochemical signals that triggers the formation of new alveoli in the lungs of mice. It turned out that it is generated by specialized cells of the endothelium lining the inner surface of the blood vessels of the lungs.
According to the head of the study, Professor Shahin Rafii, there is an assumption that human lungs have the ability to regenerate until they lose it due to COPD, cancer or other serious chronic diseases.
During earlier work, Professor Rafia's group identified growth factors that control the regeneration of the liver and bone marrow: in both cases, the main growth factors were produced by vascular endothelial cells, on the basis of which they were called "angiocrine factors". The result of the latest work of scientists was the identification of the same phenomenon in lung tissue.
The results of earlier work showed that when one lung is removed from a mouse, the size of the second one can increase by 80%, which makes it possible to almost completely compensate for the loss of one of the pair of organs. However, this phenomenon is observed only in injuries that simultaneously lead to a decrease in lung volume. In this case, the blood vessels of the preserved lung receive a signal to start the process of forming new alveoli.
To identify this signal, the researchers removed the left lungs of mice and studied the biochemical aspects of the process of subsequent regeneration of the preserved right lungs. They found that removal of the left lung activates receptors on the surface of the endothelial vessels of the preserved lung that respond to vascular endothelial growth factor (VEGF) and the main fibroblast growth factor (FGF-2). Activation of these receptors stimulates the synthesis of another protein – matrix metalloproteinase 14 (MMP14). Researchers have demonstrated that by releasing epidermal growth factors (EGF), it is MMP14 that triggers the formation of new lung tissue.
With selective inactivation of VEGF and FGF-2 receptors in endothelial cells, due to the absence of MMP14, lung regeneration did not occur. At the same time, transplantation of normal endothelial cells to such animals restored MMP14 production, triggering the formation of new functional alveoli.
In the future, researchers are going to decipher the primary signals that provide the initial stage of activation of the endothelium of the pulmonary vessels. They also plan to find out whether the processes they have identified take place in the human lungs.
Combined, the results of two studies open up new prospects in the treatment of severe chronic lung diseases that worsen the quality of life of a huge number of people and are one of the main causes of mortality.
Articles by Pooja A. Kumar et al. Distal Airway Stem Cells Yield Alveoli In Vitro and during Lung Regeneration following H1N1 Influenza Infection and Bi-Sen Ding et al. Endothelial-Derived Angiocrine Signals Induce and Sustain Regenerative Lung Alveolarization are published in the journal Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on materials from Weill Cornell Medical College: Lung Regeneration Closer to Reality With New Discovery by Weill Cornell Medical College Researchers and Harvard Medical School: Lung Stem Cells Offer Therapeutic Clues.
Portal "Eternal youth" http://vechnayamolodost.ru
01.10.2011