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Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.

Identifieur interne : 001935 ( Main/Exploration ); précédent : 001934; suivant : 001936

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.

Auteurs : Fermín Sánchez-Guijo [Espagne] ; Mariano García-Arranz [Espagne] ; Miriam L Pez-Parra [Espagne] ; Pablo Monedero [Espagne] ; Carmen Mata-Martínez [Espagne] ; Arnoldo Santos [Espagne] ; Víctor Sagredo [Espagne] ; José-Manuel Álvarez-Avello [Espagne] ; José Eugenio Guerrero [Espagne] ; César Pérez-Calvo [Espagne] ; Miguel-Vicente Sánchez-Hernández [Espagne] ; José Luis Del-Pozo [Espagne] ; Enrique J. Andreu [Espagne] ; María-Eugenia Fernández-Santos [Espagne] ; Barbara Soria-Juan [Espagne] ; Luis M. Hernández-Blasco [Espagne] ; Etelvina Andreu [Espagne] ; José M. Sempere [Espagne] ; Agustín G. Zapata [Espagne] ; José M. Moraleda [Espagne] ; Bernat Soria [Espagne] ; Francisco Fernández-Avilés [Espagne] ; Damián García-Olmo [Espagne] ; Felipe Pr Sper [Espagne]

Source :

RBID : pubmed:32838232

Abstract

Background

Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.

Methods

Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10

Findings

First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.

Interpretation

Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.

Funding

None.


DOI: 10.1016/j.eclinm.2020.100454
PubMed: 32838232
PubMed Central: PMC7348610


Affiliations:


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<name sortKey="Guerrero, Jose Eugenio" sort="Guerrero, Jose Eugenio" uniqKey="Guerrero J" first="José Eugenio" last="Guerrero">José Eugenio Guerrero</name>
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<name sortKey="Sanchez Hernandez, Miguel Vicente" sort="Sanchez Hernandez, Miguel Vicente" uniqKey="Sanchez Hernandez M" first="Miguel-Vicente" last="Sánchez-Hernández">Miguel-Vicente Sánchez-Hernández</name>
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<name sortKey="Del Pozo, Jose Luis" sort="Del Pozo, Jose Luis" uniqKey="Del Pozo J" first="José Luis" last="Del-Pozo">José Luis Del-Pozo</name>
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<name sortKey="Fernandez Santos, Maria Eugenia" sort="Fernandez Santos, Maria Eugenia" uniqKey="Fernandez Santos M" first="María-Eugenia" last="Fernández-Santos">María-Eugenia Fernández-Santos</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
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<country xml:lang="fr">Espagne</country>
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<name sortKey="Soria Juan, Barbara" sort="Soria Juan, Barbara" uniqKey="Soria Juan B" first="Barbara" last="Soria-Juan">Barbara Soria-Juan</name>
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<name sortKey="Hernandez Blasco, Luis M" sort="Hernandez Blasco, Luis M" uniqKey="Hernandez Blasco L" first="Luis M" last="Hernández-Blasco">Luis M. Hernández-Blasco</name>
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<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
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<name sortKey="Andreu, Etelvina" sort="Andreu, Etelvina" uniqKey="Andreu E" first="Etelvina" last="Andreu">Etelvina Andreu</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
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<name sortKey="Sempere, Jose M" sort="Sempere, Jose M" uniqKey="Sempere J" first="José M" last="Sempere">José M. Sempere</name>
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<wicri:regionArea>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante</wicri:regionArea>
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<name sortKey="Zapata, Agustin G" sort="Zapata, Agustin G" uniqKey="Zapata A" first="Agustín G" last="Zapata">Agustín G. Zapata</name>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
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<nlm:affiliation>Department of Cell Biology, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
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<wicri:regionArea>Department of Cell Biology, Universidad Complutense, Madrid</wicri:regionArea>
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<name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
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<nlm:affiliation>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain.</nlm:affiliation>
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<wicri:regionArea>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia</wicri:regionArea>
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<name sortKey="Soria, Bernat" sort="Soria, Bernat" uniqKey="Soria B" first="Bernat" last="Soria">Bernat Soria</name>
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<nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:affiliation>Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain.</nlm:affiliation>
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<wicri:regionArea>Institute of Bioengineering, Universidad Miguel Hernández, Alicante</wicri:regionArea>
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<name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<nlm:affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<nlm:affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<affiliation wicri:level="3">
<nlm:affiliation>Department of Medicine, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Medicine, Universidad Complutense, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<author>
<name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
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<name sortKey="Sanchez Guijo, Fermin" sort="Sanchez Guijo, Fermin" uniqKey="Sanchez Guijo F" first="Fermín" last="Sánchez-Guijo">Fermín Sánchez-Guijo</name>
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<country xml:lang="fr">Espagne</country>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
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<nlm:affiliation>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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<wicri:regionArea>CIBER de Enfermedades Respiratorias CIBERES, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<nlm:affiliation>Intensive Care Unit, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Unit, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca</wicri:regionArea>
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<nlm:affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
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<nlm:affiliation>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Anesthesia, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca</wicri:regionArea>
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<nlm:affiliation>Infectious Diseases Division, Microbiology Department, Clínica Universidad de Navarra, Spain.</nlm:affiliation>
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<author>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
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<name sortKey="Fernandez Santos, Maria Eugenia" sort="Fernandez Santos, Maria Eugenia" uniqKey="Fernandez Santos M" first="María-Eugenia" last="Fernández-Santos">María-Eugenia Fernández-Santos</name>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
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<name sortKey="Soria Juan, Barbara" sort="Soria Juan, Barbara" uniqKey="Soria Juan B" first="Barbara" last="Soria-Juan">Barbara Soria-Juan</name>
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<nlm:affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<name sortKey="Hernandez Blasco, Luis M" sort="Hernandez Blasco, Luis M" uniqKey="Hernandez Blasco L" first="Luis M" last="Hernández-Blasco">Luis M. Hernández-Blasco</name>
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<nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
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<author>
<name sortKey="Andreu, Etelvina" sort="Andreu, Etelvina" uniqKey="Andreu E" first="Etelvina" last="Andreu">Etelvina Andreu</name>
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<nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
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<author>
<name sortKey="Sempere, Jose M" sort="Sempere, Jose M" uniqKey="Sempere J" first="José M" last="Sempere">José M. Sempere</name>
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<nlm:affiliation>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante</wicri:regionArea>
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<author>
<name sortKey="Zapata, Agustin G" sort="Zapata, Agustin G" uniqKey="Zapata A" first="Agustín G" last="Zapata">Agustín G. Zapata</name>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<nlm:affiliation>Department of Cell Biology, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Cell Biology, Universidad Complutense, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<name sortKey="Moraleda, Jose M" sort="Moraleda, Jose M" uniqKey="Moraleda J" first="José M" last="Moraleda">José M. Moraleda</name>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
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<nlm:affiliation>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain.</nlm:affiliation>
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<name sortKey="Soria, Bernat" sort="Soria, Bernat" uniqKey="Soria B" first="Bernat" last="Soria">Bernat Soria</name>
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<nlm:affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante</wicri:regionArea>
<wicri:noRegion>Alicante</wicri:noRegion>
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<nlm:affiliation>Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
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<name sortKey="Fernandez Aviles, Francisco" sort="Fernandez Aviles, Francisco" uniqKey="Fernandez Aviles F" first="Francisco" last="Fernández-Avilés">Francisco Fernández-Avilés</name>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
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<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid</wicri:regionArea>
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<nlm:affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
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</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Department of Medicine, Universidad Complutense, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Medicine, Universidad Complutense, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Garcia Olmo, Damian" sort="Garcia Olmo, Damian" uniqKey="Garcia Olmo D" first="Damián" last="García-Olmo">Damián García-Olmo</name>
<affiliation wicri:level="3">
<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="4">
<nlm:affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid</wicri:regionArea>
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<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
<orgName type="university">Université autonome de Madrid</orgName>
</affiliation>
<affiliation wicri:level="3">
<nlm:affiliation>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Pr Sper, Felipe" sort="Pr Sper, Felipe" uniqKey="Pr Sper F" first="Felipe" last="Pr Sper">Felipe Pr Sper</name>
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<nlm:affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>RETIC TerCel, ISCIII, Madrid</wicri:regionArea>
<placeName>
<settlement type="city">Madrid</settlement>
<region nuts="2" type="region">Communauté de Madrid</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Grupo Español de Trasplante y Terapia Celular (GETH)</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</nlm:affiliation>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
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<series>
<title level="j">EClinicalMedicine</title>
<idno type="eISSN">2589-5370</idno>
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<date when="2020" type="published">2020</date>
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<div type="abstract" xml:lang="en">
<p>
<b>Background</b>
</p>
<p>Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>Methods</b>
</p>
<p>Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>Findings</b>
</p>
<p>First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>Interpretation</b>
</p>
<p>Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>Funding</b>
</p>
<p>None.</p>
</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM">
<PMID Version="1">32838232</PMID>
<DateRevised>
<Year>2021</Year>
<Month>01</Month>
<Day>27</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">2589-5370</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>25</Volume>
<PubDate>
<Year>2020</Year>
<Month>Aug</Month>
</PubDate>
</JournalIssue>
<Title>EClinicalMedicine</Title>
<ISOAbbreviation>EClinicalMedicine</ISOAbbreviation>
</Journal>
<ArticleTitle>Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study.</ArticleTitle>
<Pagination>
<MedlinePgn>100454</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.eclinm.2020.100454</ELocationID>
<Abstract>
<AbstractText Label="Background" NlmCategory="UNASSIGNED">Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.</AbstractText>
<AbstractText Label="Methods" NlmCategory="UNASSIGNED">Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 10
<sup>6</sup>
(IQR 0.50 × 10
<sup>6</sup>
) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.</AbstractText>
<AbstractText Label="Findings" NlmCategory="UNASSIGNED">First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.</AbstractText>
<AbstractText Label="Interpretation" NlmCategory="UNASSIGNED">Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.</AbstractText>
<AbstractText Label="Funding" NlmCategory="UNASSIGNED">None.</AbstractText>
<CopyrightInformation>© 2020 The Authors.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Sánchez-Guijo</LastName>
<ForeName>Fermín</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>García-Arranz</LastName>
<ForeName>Mariano</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>López-Parra</LastName>
<ForeName>Miriam</ForeName>
<Initials>M</Initials>
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<Affiliation>Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Monedero</LastName>
<ForeName>Pablo</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Mata-Martínez</LastName>
<ForeName>Carmen</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
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<LastName>Santos</LastName>
<ForeName>Arnoldo</ForeName>
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</AffiliationInfo>
<AffiliationInfo>
<Affiliation>CIBER de Enfermedades Respiratorias CIBERES, Madrid, Spain.</Affiliation>
</AffiliationInfo>
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<ForeName>Víctor</ForeName>
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</AffiliationInfo>
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<LastName>Álvarez-Avello</LastName>
<ForeName>José-Manuel</ForeName>
<Initials>JM</Initials>
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<Affiliation>Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Guerrero</LastName>
<ForeName>José Eugenio</ForeName>
<Initials>JE</Initials>
<AffiliationInfo>
<Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
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<LastName>Pérez-Calvo</LastName>
<ForeName>César</ForeName>
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</AffiliationInfo>
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<LastName>Sánchez-Hernández</LastName>
<ForeName>Miguel-Vicente</ForeName>
<Initials>MV</Initials>
<AffiliationInfo>
<Affiliation>Department of Anesthesia, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Del-Pozo</LastName>
<ForeName>José Luis</ForeName>
<Initials>JL</Initials>
<AffiliationInfo>
<Affiliation>Infectious Diseases Division, Microbiology Department, Clínica Universidad de Navarra, Spain.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Andreu</LastName>
<ForeName>Enrique J</ForeName>
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<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
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<ForeName>María-Eugenia</ForeName>
<Initials>ME</Initials>
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<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Soria-Juan</LastName>
<ForeName>Barbara</ForeName>
<Initials>B</Initials>
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<Affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Hernández-Blasco</LastName>
<ForeName>Luis M</ForeName>
<Initials>LM</Initials>
<AffiliationInfo>
<Affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Andreu</LastName>
<ForeName>Etelvina</ForeName>
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<AffiliationInfo>
<Affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sempere</LastName>
<ForeName>José M</ForeName>
<Initials>JM</Initials>
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<Affiliation>Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Zapata</LastName>
<ForeName>Agustín G</ForeName>
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<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Cell Biology, Universidad Complutense, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Moraleda</LastName>
<ForeName>José M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Soria</LastName>
<ForeName>Bernat</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Fernández-Avilés</LastName>
<ForeName>Francisco</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Medicine, Universidad Complutense, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>García-Olmo</LastName>
<ForeName>Damián</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Prósper</LastName>
<ForeName>Felipe</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>RETIC TerCel, ISCIII, Madrid, Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Grupo Español de Trasplante y Terapia Celular (GETH), Spain.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain.</Affiliation>
</AffiliationInfo>
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<Month>07</Month>
<Day>10</Day>
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<KeywordList Owner="NOTNLM">
<Keyword MajorTopicYN="N">COVID-19</Keyword>
<Keyword MajorTopicYN="N">Case series</Keyword>
<Keyword MajorTopicYN="N">Cellular therapy</Keyword>
<Keyword MajorTopicYN="N">Mechanical ventilation</Keyword>
<Keyword MajorTopicYN="N">Mesenchymal stromal cells</Keyword>
<Keyword MajorTopicYN="N">Pneumonia</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV-2</Keyword>
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<CoiStatement>Dr. Sanchez-Guijo reports grants and personal fees from Novartis, personal fees from BMS, Pfizer, Incyte, Gilead, Roche and Amgen, outside the submitted work; Dr. López-Parra reports personal fees from Gilead, Novartis, BMS and Janssen, outside the submitted work. Dr. JL del Pozo reports grants from Novartis and personal fees from Novartis, Pfizer, Gilead and Roche, outside the submitted work; Dr. Moraleda reports personal fees and other from Gilead, grants and personal fees from Jazz Pharma, and personal fees from Novartis and from Sandoz, outside the submitted work. Dr. García-Olmo has received personal fees from Takeda, outside the submitted work; Dr. Prosper reports personal fees from Oryzon Genomics, and from Janssen, outside the submitted work; Dr. García-Arranz and Dr. García-Olmo have applied for two patents related with this study entitled “Identification and isolation of multipotent cells from nonosteochondral mesenchymal tissue” (WO 2006/057649) and “Use of adipose tissue-derived stromal stem cells in treating fistula” (WO 2006/136244), and both are shareholders of Biosurgery, an educational company providing services to Takeda. All other authors declare no conflict of interest.</CoiStatement>
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