Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 9; p. 2015
• Main Authors: Tovar, Isabel, Guerrero, Rosa, López-Peñalver, Jesús J, Expósito, José, Ruiz de Almodóvar, José Mariano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.09.2020; MDPI
• Subjects: Adult respiratory distress syndrome; annexin A1; Annexin A1 - metabolism; Antitumor activity; Betacoronavirus - isolation & purification; Cancer therapies; Cell therapy; Clinical trials; Clinical Trials as Topic; Coronavirus Infections - therapy; Coronavirus Infections - virology; COVID-19; exosome; Exosomes; Exosomes - metabolism; experimental radiotherapy; Gamma Rays; Genotype & phenotype; Health aspects; Humans; Hypoxia; Kinases; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - radiation effects; Mesenchyme; Metastases; Metastasis; Pandemics; Physiological aspects; Pneumonia, Viral - therapy; Pneumonia, Viral - virology; Proteins; Radiation therapy; radiobiology; Respiratory distress syndrome; Respiratory Distress Syndrome - pathology; Respiratory Distress Syndrome - therapy; Respiratory Distress Syndrome - virology; Review; SARS-CoV-2; Senescence; Severe acute respiratory syndrome coronavirus 2; Stem cell transplantation; Stem cells; Tumors; Spain; COVID-19; radiobiology; annexin A1; cell therapy; mesenchymal stem cells; exosome; acute respiratory-distress syndrome; experimental radiotherapy
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9092015

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.