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

• Published in: Stem cell research & therapy Vol. 11; no. 1; pp. 116 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.03.2020; BioMed Central; BMC
• Subjects: Adult respiratory distress syndrome; Analysis; Antibiotics; ARDS; Bone marrow; Cell therapy; Cryopreservation; E coli; Escherichia coli; Infection; Isolation; Mesenchymal stem cell; Mesenchymal stem cells; Mesenchyme; Ostomy; Passage; Pneumonia; Production management; Respiratory distress syndrome; Setting (Literature); Stem cells; Stromal cells; Time; Umbilical cord; Ventilators; United Kingdom; United Kingdom > UK; Ireland; Mesenchymal stem cell; Pneumonia; Antibiotics; Passage; Cryopreservation; ARDS
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-020-01624-8

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. 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. 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. 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.