The bone marrow niche components are adversely affected in sepsis
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Molecular Biomedicine
RESEARCH
Open Access
The bone marrow niche components are adversely affected in sepsis Fan Yin1, Han Qian1, Caiwen Duan2* and Botao Ning1*
Abstract Multiple organ dysfunction is an important cause of death in patients with sepsis. Currently, few studies have focused on the impact of sepsis on bone marrow (BM), especially on the cell components of BM niche. In this study, we performed mouse sepsis models by intraperitoneal injection of LPS and cecal ligation and puncture (CLP). The changes of niche major components in the mouse BM among vascular structures, mesenchymal stem cells and Treg cells were observed and analyzed. The results showed that pathological changes in BM was earlier and more prominent than in other organs, and various cell components of the BM niche changed significantly, of which vascular endothelial cells increased transiently with vascular remodeling and the regulatory T cells decreased over a long period of time. These results indicated that the components of the BM niche underwent series of adaptive changes in sepsis. Keywords: Bone marrow niche, Sepsis, Lipopolysaccharide (LPS), Mouse model
Introduction Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection, and is the leading cause of death in intensive care unit (ICU) [1, 2]. Septic shock frequently cause multi-organ dysfunction [3]. Among these affected organs, it is not clear which was affected initially and most significantly. Clinically, we tend to focus on the conditions of infection, sepsisinduced cardiomyopathy, disseminated intravascular coagulation, and the injury to respiratory system, liver and kidney, while ignored alterations of bone marrow (BM) during sepsis, especially the changes in BM niche. Previous studies have suggested that key organs such as kidney and gut are vulnerable during sepsis [4, 5], interactions between organs during sepsis play a pivotal role in sepsis pathogenesis [3]. Notably, BM plays an equally important part in sepsis [6], which contains hematopoietic * Correspondence: [email protected]; [email protected] 2 Department of Translational Institution, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, Shanghai, China 1 Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, 1678 Dongfang Road, Shanghai, China
progenitor cells and supporting niche cells. Sepsismediated BM suppression often leads to myeloid cell differentiation disorders, and myeloid cell dysfunction is associated with acquired immunodeficiency in sepsis [7]. Niche components of BM do not participate in hematopoiesis, but support hematopoiesis and maintain niche homeostasis. About sepsis, there has been so far much research focused on the regulation of the BM hematopoiesis by the niche component [8, 9], but few dealt with the changes of endothelial cells (ECs), mesenchymal stem cells (MSCs) and immune cells in BM niche. To illustrate the sepsis induc
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