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The efficacy of mesenchymal stem cell therapy in experimental sepsis induced by carbapenem-resistant K. pneumoniae in neutropenic mice model.
European Journal of Clinical Microbiology & Infectious Diseases ( IF 4.5 ) Pub Date : 2020-04-30 , DOI: 10.1007/s10096-020-03910-y
Gokcen Dinc 1, 2 , Esma Eren 3 , Olgun Kontas 4 , Mehmet Doganay 5
Affiliation  

Especially in recent years, the intensive use of antibiotics has caused multiple drug resistance in Klebsiella pneumoniae. In the absence of a new antibiotic, alternative treatment options have emerged. The aim of this study was to investigate the efficacy of mesenchymal stem cell (MSC) treatment of carbapenem-resistant K. pneumoniae sepsis in neutropenic murine model. BALB-c mice were divided into two groups as control (positive and negative) and treatment groups (colistin, colistin + MSC, MSC) after the development of neutropenia with cyclophosphamide. Sepsis was developed in mice by intraperitoneal injection of carbapenem-resistant K. pneumoniae. Three hours after inoculation of the bacteria, colistin and MSC were given in the treatment groups intraperitoneally. Colistin injection was repeated every 12 h, while MSC was administered as 2nd dose after 48 h. Mice were sacrificed at 48 and 96 h. The right lung and half of the liver were quantitatively cultured, and the bacterial load was calculated as cfu/g. The left lung, the other half of the liver tissue, and both kidneys were evaluated histopathologically. IL-6 and TNF-α cytokine levels in mouse sera were determined by ELISA. Bacterial loads in lung and liver tissues of neutropenic mice were lower in the MSC + colistin-treated group at 48 and 96 h compared to colistin and MSC monotherapy groups. Also, bacterial eradication was started the earliest in MSC + colistin group. It was concluded that combining colistin with MSC provided improved therapeutic effects compared to colistin or MSC monotherapy.



中文翻译:

间充质干细胞疗法在中性粒细胞减少症模型中对碳青霉烯耐药的肺炎克雷伯菌引起的实验性脓毒症中的疗效。

特别是近年来,抗生素的大量使用已引起肺炎克雷伯菌的多重耐药性。在没有新抗生素的情况下,出现了替代治疗选择。这项研究的目的是研究中性粒细胞减少性小鼠模型中间充质干细胞(MSC)治疗对碳青霉烯耐药的肺炎克雷伯菌败血症的疗效。在用环磷酰胺发展嗜中性白血球减少症后,将BALB-c小鼠分为对照组(阳性和阴性)和治疗组(共利斯汀,粘菌素+ MSC,MSC)两组。通过腹腔注射对碳青霉烯耐药的肺炎克雷伯氏菌在小鼠中产生败血症。细菌接种后三小时,腹膜内给予治疗组粘菌素和MSC。每12小时重复一次Colistin注射,而48小时后以第二剂量给予MSC。在48和96小时处死小鼠。定量培养右肺和肝的一半,细菌载量计算为cfu / g。组织病理学评价左肺,肝组织的另一半和两个肾脏。通过ELISA测定小鼠血清中的IL-6和TNF-α细胞因子水平。与粘菌素和MSC单药治疗组相比,MSC +粘菌素治疗组在48 h和96 h时,中性粒细胞减少症小鼠的肺和肝组织中的细菌负荷较低。此外,最早在MSC + colistin组中开始消灭细菌。

更新日期:2020-04-30
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