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Horie, S,Masterson, C,Brady, J,Loftus, P,Horan, E,O'Flynn, L,Elliman, S,Barry, F,O'Brien, T,Laffey, JG,O'Toole, D
2020
March
Stem Cell Research & Therapy
Umbilical cord-derived CD362(+) mesenchymal stromal cells for E. coli pneumonia: impact of dose regimen, passage, cryopreservation, and antibiotic therapy
Published
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Mesenchymal stem cell ARDS Pneumonia Cryopreservation Passage Antibiotics ACUTE LUNG INJURY STEM-CELLS HYPERCAPNIC ACIDOSIS BACTERIAL CLEARANCE IMPROVES SURVIVAL DELIVERY SHOCK MICE
11
BackgroundMesenchymal 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.MethodsAdult 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 (0h vs 6h post-injury vs 6h+12h) following E. coli installation.ResultsCD362(+) 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 6h+12h, following E. coli instillation.ConclusionsThese 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.
10.1186/s13287-020-01624-8
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