Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 31 July 2020 / Approved: 2 August 2020 / Online: 2 August 2020 (14:54:24 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Cells 2020, 9, 2015
DOI: 10.3390/cells9092015

Abstract

Previously we have shown that the combination of radiotherapy with human-umbilical-cord-derived mesenchymal stem-cell therapy significantly reduces the size of the xenotumours in mice, both in the directly irradiated tumour and in the distant non-irradiated tumour or in its metastasis. We have also shown that exosomes secreted from mesenchymal stem-cells pre-irradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from non-irradiated mesenchymal cells and also that proteins, exosomes and microvesicles secreted by mesenchymal cells suffer a dramatic change when cells are activated or non-activated, with the amount of protein present in the exosomes of the pre-irradiated cells being 1.5-fold times greater compared to those from non-irradiated cells. This finding correlates with a dramatic increase in the anti-tumour activity of the exosomes secreted by pre-irradiated mesenchymal-cells. After the proteomic analysis of the load of the exosomes released from both irradiated and non-irradiated 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 which is characteristic of acute-distress-respiratory syndrome, we have designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by COVID-19, require the care of an intensive care unit for patients with life-threatening conditions. With this hypothesis, we would seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

Subject Areas

Experimental radiotherapy; radiobiology; Mesenchymal stem cells; Cell therapy; Exosome; Annexin A1; Acute-respiratory-distress-syndrome; COVID-19

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