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Review

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

1
Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain
2
Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain
3
Unidad de Radiología Experimental, Centro de Investigación Biomédica, Universidad de Granada, PTS Granada, 18016 Granada, Spain
4
Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Granada, PTS Granada, 18016 Granada, Spain
5
Centro de Investigación Biomédica, Universidad de Granad, PTS Granada, 18016 Granada, Spain
*
Author to whom correspondence should be addressed.
Cells 2020, 9(9), 2015; https://doi.org/10.3390/cells9092015
Received: 31 July 2020 / Revised: 29 August 2020 / Accepted: 31 August 2020 / Published: 2 September 2020
(This article belongs to the Special Issue Stem Cells and Irradiation)
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. View Full-Text
Keywords: experimental radiotherapy; radiobiology; mesenchymal stem cells; cell therapy; exosome; annexin A1; acute respiratory-distress syndrome; COVID-19 experimental radiotherapy; radiobiology; mesenchymal stem cells; cell therapy; exosome; annexin A1; acute respiratory-distress syndrome; COVID-19
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MDPI and ACS Style

Tovar, I.; Guerrero, R.; López-Peñalver, J.J.; Expósito, J.; Ruiz de Almodóvar, J.M. Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. Cells 2020, 9, 2015. https://doi.org/10.3390/cells9092015

AMA Style

Tovar I, Guerrero R, López-Peñalver JJ, Expósito J, Ruiz de Almodóvar JM. Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. Cells. 2020; 9(9):2015. https://doi.org/10.3390/cells9092015

Chicago/Turabian Style

Tovar, Isabel, Rosa Guerrero, Jesús J. López-Peñalver, José Expósito, and José M. Ruiz de Almodóvar 2020. "Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome" Cells 9, no. 9: 2015. https://doi.org/10.3390/cells9092015

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