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.

中文翻译：

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脐带来源的CD362 +间充质基质细胞治疗大肠杆菌性肺炎：剂量方案，传代，冷冻保存和抗生素治疗的影响。

间充质基质细胞（MSCs）显示出对急性呼吸窘迫综合征（ARDS）和败血症的巨大希望。但是，用于MSC分离的标准方法会产生高度异质的细胞群，而骨髓（BM）构成了有限且难以访问的MSC来源。此外，细胞制造方面的考虑因素和临床设置实用性仍有待探索。成年雄性大鼠接受大肠杆菌诱导的肺炎，并使用多种细胞产生和临床相关性考虑因素给予CD362 +脐带（UC）-hMSC。在系列1中，将动物灌入大肠杆菌并随机接受异质BM或UC-hMSC或CD362 + UC-hMSC。随后的系列研究了伴随抗生素治疗的影响，MSC治疗性冷冻保存（冷冻保存与新鲜CD362 + UC-hMSCs），细胞传代对功效的影响（传代3次，5次，7次，10次）以及细胞治疗的延迟（损伤后0h对6h和6h +大肠杆菌安装后12 h）。CD362 + UC-hMSC与异源MSC在减少大肠杆菌诱导的急性肺损伤，改善氧合作用，减少细菌负荷，减少组织损伤和改善炎症标志物水平方面一样有效。冷冻保存的CD362 + UC-hMSC再现了这种功效，减弱了大肠杆菌诱导的损伤，但是治疗相关性并未延伸到所有指标的第3代。CD362 + UC-hMSCs在存在抗生素治疗的情况下仍保持效力，并在大肠杆菌滴注后6小时+ 12小时将其从大肠杆菌中救出。