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Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy

BACKGROUND: Mesenchymal stromal cells (MSCs) demonstrate considerable promise for acute respiratory distress syndrome (ARDS) and sepsis. However, standard approaches to MSC isolation generate highly heterogeneous cell populations, while bone marrow (BM) constitutes a limited and difficult to access...

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Autores principales: Horie, Shahd, Masterson, Claire, Brady, Jack, Loftus, Paul, Horan, Emma, O’Flynn, Lisa, Elliman, Steve, Barry, Frank, O’Brien, Timothy, Laffey, John G., O’Toole, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071745/
https://www.ncbi.nlm.nih.gov/pubmed/32169108
http://dx.doi.org/10.1186/s13287-020-01624-8
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author Horie, Shahd
Masterson, Claire
Brady, Jack
Loftus, Paul
Horan, Emma
O’Flynn, Lisa
Elliman, Steve
Barry, Frank
O’Brien, Timothy
Laffey, John G.
O’Toole, Daniel
author_facet Horie, Shahd
Masterson, Claire
Brady, Jack
Loftus, Paul
Horan, Emma
O’Flynn, Lisa
Elliman, Steve
Barry, Frank
O’Brien, Timothy
Laffey, John G.
O’Toole, Daniel
author_sort Horie, Shahd
collection PubMed
description BACKGROUND: Mesenchymal stromal cells (MSCs) demonstrate considerable promise for acute respiratory distress syndrome (ARDS) and sepsis. However, standard approaches to MSC isolation generate highly heterogeneous cell populations, while bone marrow (BM) constitutes a limited and difficult to access MSC source. Furthermore, a range of cell manufacturing considerations and clinical setting practicalities remain to be explored. METHODS: Adult male rats were subject to E. coli-induced pneumonia and administered CD362(+) umbilical cord (UC)-hMSCs using a variety of cell production and clinical relevance considerations. In series 1, animals were instilled with E. coli and randomized to receive heterogeneous BM or UC-hMSCs or CD362(+) UC-hMSCs. Subsequent series examined the impact of concomitant antibiotic therapy, MSC therapeutic cryopreservation (cryopreserved vs fresh CD362(+) UC-hMSCs), impact of cell passage on efficacy (passages 3 vs 5 vs 7 vs 10), and delay of administration of cell therapy (0 h vs 6 h post-injury vs 6 h + 12 h) following E. coli installation. RESULTS: CD362(+) UC-hMSCs were as effective as heterogonous MSCs in reducing E. coli-induced acute lung injury, improving oxygenation, decreasing bacterial load, reducing histologic injury, and ameliorating inflammatory marker levels. Cryopreserved CD362(+) UC-hMSCs recapitulated this efficacy, attenuating E. coli-induced injury, but therapeutic relevance did not extend beyond passage 3 for all indices. CD362(+) UC-hMSCs maintained efficacy in the presence of antibiotic therapy and rescued the animal from E. coli injury when delivered at 6 h + 12 h, following E. coli instillation. CONCLUSIONS: These translational studies demonstrated the efficacy of CD362(+) UC-hMSCs, where they decreased the severity of E. coli-induced pneumonia, maintained efficacy following cryopreservation, were more effective at early passage, were effective in the presence of antibiotic therapy, and could continue to provide benefit at later time points following E. coli injury.
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spelling pubmed-70717452020-03-18 Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy Horie, Shahd Masterson, Claire Brady, Jack Loftus, Paul Horan, Emma O’Flynn, Lisa Elliman, Steve Barry, Frank O’Brien, Timothy Laffey, John G. O’Toole, Daniel Stem Cell Res Ther Research BACKGROUND: Mesenchymal stromal cells (MSCs) demonstrate considerable promise for acute respiratory distress syndrome (ARDS) and sepsis. However, standard approaches to MSC isolation generate highly heterogeneous cell populations, while bone marrow (BM) constitutes a limited and difficult to access MSC source. Furthermore, a range of cell manufacturing considerations and clinical setting practicalities remain to be explored. METHODS: Adult male rats were subject to E. coli-induced pneumonia and administered CD362(+) umbilical cord (UC)-hMSCs using a variety of cell production and clinical relevance considerations. In series 1, animals were instilled with E. coli and randomized to receive heterogeneous BM or UC-hMSCs or CD362(+) UC-hMSCs. Subsequent series examined the impact of concomitant antibiotic therapy, MSC therapeutic cryopreservation (cryopreserved vs fresh CD362(+) UC-hMSCs), impact of cell passage on efficacy (passages 3 vs 5 vs 7 vs 10), and delay of administration of cell therapy (0 h vs 6 h post-injury vs 6 h + 12 h) following E. coli installation. RESULTS: CD362(+) UC-hMSCs were as effective as heterogonous MSCs in reducing E. coli-induced acute lung injury, improving oxygenation, decreasing bacterial load, reducing histologic injury, and ameliorating inflammatory marker levels. Cryopreserved CD362(+) UC-hMSCs recapitulated this efficacy, attenuating E. coli-induced injury, but therapeutic relevance did not extend beyond passage 3 for all indices. CD362(+) UC-hMSCs maintained efficacy in the presence of antibiotic therapy and rescued the animal from E. coli injury when delivered at 6 h + 12 h, following E. coli instillation. CONCLUSIONS: These translational studies demonstrated the efficacy of CD362(+) UC-hMSCs, where they decreased the severity of E. coli-induced pneumonia, maintained efficacy following cryopreservation, were more effective at early passage, were effective in the presence of antibiotic therapy, and could continue to provide benefit at later time points following E. coli injury. BioMed Central 2020-03-13 /pmc/articles/PMC7071745/ /pubmed/32169108 http://dx.doi.org/10.1186/s13287-020-01624-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Horie, Shahd
Masterson, Claire
Brady, Jack
Loftus, Paul
Horan, Emma
O’Flynn, Lisa
Elliman, Steve
Barry, Frank
O’Brien, Timothy
Laffey, John G.
O’Toole, Daniel
Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
title Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
title_full Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
title_fullStr Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
title_full_unstemmed Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
title_short Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
title_sort umbilical cord-derived cd362(+) mesenchymal stromal cells for e. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071745/
https://www.ncbi.nlm.nih.gov/pubmed/32169108
http://dx.doi.org/10.1186/s13287-020-01624-8
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