The efficacy of mesenchymal stem cell therapy in experimental sepsis induced by carbapenem-resistant K. pneumoniae in ne
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ORIGINAL ARTICLE
The efficacy of mesenchymal stem cell therapy in experimental sepsis induced by carbapenem-resistant K. pneumoniae in neutropenic mice model Gokcen Dinc 1,2
&
Esma Eren 3 & Olgun Kontas 4 & Mehmet Doganay 5
Received: 28 January 2020 / Accepted: 13 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords Experimental neutropenia . K. pneumoniae . Mesenchymal stem cell . Sepsis
Introduction Sepsis is a life-threatening progressive infectious disease. Severe sepsis may cause vascular leakage, tissue damage, multiple organ failure, and a high mortality rate. It is
* Gokcen Dinc [email protected] 1
Department of Medical Microbiology, Faculty of Medicine, Erciyes University, 38039 Kayseri, Turkey
2
Department of Molecular Microbiology, Genome and Stem Cell Centre, Erciyes University, Kayseri, Turkey
3
Department of Infectious Diseases and Clinical Microbiology, Kayseri City Hospital, Kayseri, Turkey
4
Department of Medical Pathology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
5
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
characterized by circulatory, cellular, and metabolic abnormalities associated with systemic uncontrolled inflammatory response [1–3]. Millions of patients worldwide are affected by sepsis each year, and more than a quarter of these patients are reported to have died of sepsis [4–7]. In recent yea
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