Septic shock and pneumonia triggered by SARS-CoV-2 could be treated by radiation-activated MSCs

This study, published in the journal Cells, is based on others (all of which employed experimental models) previously conducted by researchers at the Biomedical Research Centre of the University of Granada, the ‘López-Neyra’ Institute of Parasitology and Biomedicine, and the ‘Virgen de las Nieves’ University Hospital in Granada

The results are still “a long way from being applied to sick patients, for scientific and ethical reasons,” the UGR researchers explain.

Scientists from the University of Granada (UGR) and the ‘Virgen de las Nieves’ University Hospital in Granada have found that a combination of basal mesenchymal stem cells (MSCs) and radiation-activated MSCs could be used to treat septic shock and pneumonia triggered by SARS-CoV-2, the coronavirus that causes COVID-19.

This study, which builds on others previously conducted by researchers at the Biomedical Research Centre of the University of Granada, the ‘López-Neyra’ Institute of Parasitology and Biomedicine, and the ‘Virgen de las Nieves’ University Hospital in Granada, was published recently in the journal Cells. However, the results remain “a long way from being applied to sick patients, for scientific and ethical reasons,” according to the researchers.

MSCs are a type of stem cells present in a wide variety of tissues (bone marrow, blood from the human umbilical cord, skin, adipose tissue or muscle tissue, for instance). They are capable of producing different specialized cells found in the tissues of the body human. For example, they can differentiate (or specialize) into cartilage cells (chondrocytes), bone cells (osteoblasts), and fat cells (adipocytes).

In response to the COVID-19 pandemic, numerous research groups around the world believe it is possible to increase people’s biological resistance to SARS-CoV-2 by using MSC-based therapeutic procedures. At present, there are also many clinical trials underway to verify the results of this type of cell therapy among COVID-19 patients.

In previous studies, scientists from the UGR’s Biomedical Research Centre (CIBM) have demonstrated that the combination of radiation therapy and radiation- activated MSCs dramatically reduces the size of tumors implanted in murine research models (strains of mice), both in the irradiated tumor and in its metastasis.

These findings have led us to conclude that radiation-activated MSCs enhance the action of radiotherapy through the secretion of microvesicles and proteins into the extracellular medium. From there, either free or encapsulated in minuscule structures called exosomes, they reach tumor sites located at a distance from the irradiated tumor and exert powerful antitumor effects.”  

Ruiz de Almodóvar

Tumor radiosensitization

Among the substances secreted by the activated MSCs, researchers have been able to identify exosomes heavily loaded with annexin A1 as elements potentially responsible for tumor radiosensitization. The annexin A1 protein is being widely studied in infection, inflammation, and hypoxia scenarios, and its therapeutic applications have been extensively documented by the researchers who conducted the present study (reference 1).

Knowing of the pharmacological properties of annexin A1 and the epithelial and endothelial wound-healing functions characteristic of mesenchymal cells, “we believe that the combination of their different actions may be supremely important in the treatment of septic shock and pneumonia caused by SARS-CoV-2 infection,” explains Ruiz de Almodóvar.

He continues: “We therefore anticipate that the simultaneous administration of both treatments (basal MSCs and radiation-activated MSCs) can facilitate control of the infection and inflammation processes in the lung and, by exosome transfer via blood and lymphatic flow, solve or mitigate the problems of disseminated intravascular coagulation and sepsis, which cause multiple organ dysfunction syndrome and are life-threatening among patients severely affected by COVID-19. ”

The researchers from the UGR and the ‘Virgen de las Nieves’ Hospital emphasize that these results “are simply a hypothesis and we need to carry out more experimental work and secure official approval of the treatment. But, as soon as we are sure that treatment with radiation-activated MSCs is safe and effective, we will be able to offer this cell therapy to patients affected by COVID-19.”