Department of hematology of the Second Hospital, Institute of Biotherapy for Hematological Malignancies, Shandong University-Karolinska Institute Collaborative Laboratory for Stem Cell Research, Shandong University, Jinan, Shandong Province, China.
Department of Hematology, Zhaoyuan Sorting-Yingcheng Hospital, Second Hospital of Shandong University, Yantai, Shandong Province, China.
Biosci Rep. 2019 Sep 16;39(9). doi: 10.1042/BSR20182455. Print 2019 Sep 30.
The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 10 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 10/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.
本研究旨在探讨骨髓间充质干细胞（MSC）与利奈唑胺（LZD）联合应用于耐甲氧西林金黄色葡萄球菌（MRSA）感染性肺炎兔模型是否具有协同治疗作用。分离并鉴定人脐带来源的MSC（hUMSC）。通过支气管镜将 1×10 CFU MRSA 递送至右肺下叶基底段，构建肺炎兔模型。通过分析生命体征、肺部听诊、SpO2、胸部影像学、支气管镜表现、病理学、中性粒细胞百分比和炎症因子，我们验证了成功构建了 MRSA 诱导性肺炎兔模型。单次应用 LZD（50mg/kg，每日两次）治疗可改善体重、胸部影像学、支气管镜表现、组织学参数和血浆中 IL-10 浓度（0.01），减少肺部听诊，降低血浆中 IL-8、IL-6、CRP 和 TNF-α 浓度（0.01），与肺炎模型组相比，在 48 和 168 h 时。与 LZD 组相比，hUMSC（MRSA 注入后 6 和 72 h 各 1×10/kg 两次）与 LZD 的联合应用进一步增加了体重（0.05）。从胸部影像学、支气管镜表现和病理学观察到的变化表明，hUMSC 与 LZD 的联合应用比 LZD 组更显著地减轻了肺部炎症。联合组血浆中 IL-8、IL-6、CRP 和 TNF-α 水平与 LZD 组相比显著下降（0.05）。结论：hUMSC 给药可显著改善 LZD 对兔 MRSA 感染性肺炎的治疗效果。
