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Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome.
Cells. 2020 09 02; 9(9)C

Abstract

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.

Authors+Show Affiliations

Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain. Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain.Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain. Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain.Unidad de Radiología Experimental, Centro de Investigación Biomédica, Universidad de Granada, PTS Granada, 18016 Granada, Spain.Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain. Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain. Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Granada, PTS Granada, 18016 Granada, Spain.Centro de Investigación Biomédica, Universidad de Granad, PTS Granada, 18016 Granada, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

32887260

Citation

Tovar, Isabel, et al. "Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome." Cells, vol. 9, no. 9, 2020.
Tovar I, Guerrero R, López-Peñalver JJ, et al. Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. Cells. 2020;9(9).
Tovar, I., Guerrero, R., López-Peñalver, J. J., Expósito, J., & Ruiz de Almodóvar, J. M. (2020). Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. Cells, 9(9). https://doi.org/10.3390/cells9092015
Tovar I, et al. Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. Cells. 2020 09 2;9(9) PubMed PMID: 32887260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. AU - Tovar,Isabel, AU - Guerrero,Rosa, AU - López-Peñalver,Jesús J, AU - Expósito,José, AU - Ruiz de Almodóvar,José Mariano, Y1 - 2020/09/02/ PY - 2020/07/31/received PY - 2020/08/29/revised PY - 2020/08/31/accepted PY - 2020/9/5/entrez PY - 2020/9/6/pubmed PY - 2020/9/17/medline KW - COVID-19 KW - acute respiratory-distress syndrome KW - annexin A1 KW - cell therapy KW - exosome KW - experimental radiotherapy KW - mesenchymal stem cells KW - radiobiology JF - Cells JO - Cells VL - 9 IS - 9 N2 - 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. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/32887260/Rationale_for_the_Use_of_Radiation_Activated_Mesenchymal_Stromal/Stem_Cells_in_Acute_Respiratory_Distress_Syndrome_ DB - PRIME DP - Unbound Medicine ER -