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 (see reference 1), 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 (see references 2 and 3), 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 specialised cells found in the tissues of the body human. For example, they can differentiate (or specialise) 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 (reference 2), 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 tumours implanted in murine research models (strains of mice), both in the irradiated tumour 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 tumour sites located at a distance from the irradiated tumour and exert powerful antitumor effects,” explains Ruiz de Almodóvar.
Tumour radiosensitisation
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 tumour radiosensitisation. 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 emphasise 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. ”
Bibliography:
- Isabel Tovar, Rosa Guerrero, Jesús J. López-Peñalver, José Expósito, & José M. Ruiz de Almodóvar (2020), ‘Rationale for the use of radiation-activated mesenchymal stromal/stem cells in acute respiratory distress syndrome’, Cells 9. Online: doi:10.3390/cells9092015
- V. de Araújo Farias, F. O’Valle, S. Serrano-Saenz, P. Anderson, E. Andres, J. Lopez-Penalver, I. Tovar, A. Nieto, A. Santos, F. Martin, J. Expósito, F. J. Oliver & J. M. Ruiz de Almodóvar (2018), ‘Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci’, Mol Cancer 17(1), 122. Online: doi:10.1186/s12943-018-0867-0
- V. de Araújo Farias, I. Tovar, R. Del Moral, F. O’Valle, J. Expósito, F. J. Oliver and J. M. Ruiz de Almodóvar (2019), ‘Enhancing the bystander and abscopal effects to improve radiotherapy outcomes’, Front Oncol, 9, 1381. Online: doi:10.3389/fonc.2019.01381
A). SEM images of mesenchymal stem cells in culture. B) 1. Image of microvesicle (diameter: 460 nm) and 2. Cluster of exosomes (mean diameter: 140nm) secreted by MSC cells. The images were obtained using the AURIGA (Carl Zeiss SMT) high-resolution scanning electron microscope (HRSEM)
Media enquiries:
José Mariano Ruiz de Almodóvar
Professor of Radiology, University of Granada (retired)
Email: jmrdar@ugr.es
Tel.: +34 648146605
José Expósito Hernández
Associate Professor of Radiology, University of Granada, and Head of the Oncology Radiation Service, ‘Virgen de las Nieves’ University HospitalEmail: jose.exposito.sspa@juntadeandalucia.es
