Stem cells cured the lungs

Evidence of the effectiveness of cell therapy in the treatment of acute respiratory syndrome has been obtained

Phys Tech blog, Naked Science

An international team of researchers has shown for the first time that the use of stem cells can prevent long-term consequences in patients with severe inflammatory diseases of the pulmonary system. Such diseases are not only associated with high mortality, but also lead to chronic diseases and even disability in the majority of survivors.

The article was published in one of the oldest international medical journals American Journal of Respiratory and Critical Care Medicine (Simonson et al., 5-year Follow up After MSC-based Treatment of Severe Acute Respiratory Distress Syndrome). Five years ago, two patients with multiple organ failure who were on an extracorporeal membrane lung oxygenation machine with negative dynamics of clinical parameters received a mesenchymal stem cell preparation.

After administration of the drug, they experienced a sharp improvement in their condition, and then a complete recovery. A medical examination five years later revealed practically no negative consequences of the disease and, in some parameters, showed an excess of health indicators in these patients compared to their peers.

One of the complications of viral lung diseases is acute respiratory distress syndrome (ARDS). In ARDS, uncontrolled inflammation of the lungs is observed, caused by hyperreaction of the immune system, otherwise this process is called a cytokine storm. At the moment, mortality from severe ARDS is about 40 percent, while those who have had ARDS often have long-term pulmonary, neuromuscular and cognitive symptoms. This reduces the quality of their subsequent life and leads to large expenditures of the healthcare system and social support of the population.

To date, there is no effective therapy for ARDS, and treatment is mainly aimed at maintaining patients. The need for new therapeutic approaches has become especially urgent against the background of the SARS-CoV-2 virus pandemic: the direct cause of death of the majority (according to various sources, about 80 percent) of patients with Covid-19 is ARDS.

"Methods of therapy using mesenchymal stem cells have repeatedly manifested themselves. The immunoregulatory and immunosuppressive functions of cells are particularly interesting for diseases associated with systemic inflammation and activation of the immune response. Despite the fact that mesenchymal stem cells (MSCs) have long been the focus of many scientific groups, the mechanisms of action have not yet been proven, especially in the case of acute inflammation. This makes it very difficult to transfer technology to the clinic.

The results of the proof-of-concept experiment with the injection of donor mesenchymal stromal cells have shown a promising therapeutic effect for the deadly acute syndrome, which makes it possible to approach a wider application of the method in therapy," explains Pavel Volchkov, one of the study participants, head of the Laboratory of Genomic Engineering at MIPT.

– The indisputable advantage of the approach we have obtained is universality: acute respiratory distress syndrome can develop in response to different causes, for example, due to viruses of different nature, and MSCS therapy will work regardless of these causes. This will help a large group of patients to return to a full life, which is especially important in the context of the COVID-19 pandemic, because, according to some reports, ARDS is the main cause of death in coronavirus infection."

In the published work, scientists summarize the use of a new approach to the treatment of this disease using mesenchymal stem (stromal) cells. These are "immature" cells capable of differentiating into specialized ones, that is, turning into cells of various organs and tissues of mesenchymal origin. Earlier, in 2015, treatment was carried out for two patients with a severe form of the disease, for whom the risk of death was more than 95 percent.

As a result, the cells showed a high immunomodulatory ability, which led to the suppression of inflammatory processes and the restoration of lung function. A year after the treatment, both patients were able to return to full-time work. At the time of the study, their health indicators were within the limits, and in some indicators even higher than normal. And if the effectiveness and safety of cell therapy in the treatment of inflammatory diseases has already been shown in other works, then the absence of long-term negative consequences of ARDS was a pleasant surprise and was shown for the first time.

At the moment, cell therapy technologies are relatively expensive, which makes their mass application in medicine difficult. At the same time, the results of a five-year follow-up indicate not only an improvement in the quality of life of patients in the future, but also a possible significant reduction in the burden on the healthcare system, which, with the initial high cost, makes such methods economically feasible.

Sergey Rodin, associate professor of the Department of Surgical Sciences at Uppsala University (Sweden), says: "To prove the effectiveness and safety of any method, it is necessary to conduct clinical trials with a large number of patients. Conducting clinical trials involves great risks and costs. 

Additional difficulties are associated with the fact that the results of the use of mesenchymal stromal cells critically depend on the quality of the cell product.

A large volume of preliminary data obtained first in animal models of ARDS, and then in the treatment of patients with ARDS in the framework of our treatment project on compassionate use basis (last hope) and in other countries, combined with the difficult situation with Covid–19, finally convinced the Swedish regulatory authorities to grant permission for a clinical trial, which began in the Academic Hospital in Uppsala."

Thus, scientists have received confirmation of the effectiveness of cell therapy for the treatment of ARDS and the prevention of its long-term complications. Clinical studies are required for widespread use of this method, and they have already begun. The tests will determine the safety and effectiveness of the new method in comparison with placebo control and will allow a deeper understanding of the molecular mechanisms of the influence of mesenchymal stem cells on the human immune system. 

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