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.

Highlights

  • 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]

  • (See figure on previous page.) Fig. 1 bone marrow (BM) undergoes significant histological changes after LPS challenge. a Macroscopic images of BM, lung, liver and kidney from 8-week-old control and LPS D1 mice. b, c, d, e, f, g Histological analysis by Hematoxylin and eosin (H&E) staining in the BM (BM) (b), lung (c), kidney (d), liver (e), intestine (f) and heart (g) of mice sepsis model prepared by intraperitoneal injection of LPS at 12 h, 24 h and 72 h after treatment

  • Sepsis-mediated changes in BM niche components could have a profound effect on hematopoiesis, and may be one of the pathogenesis of sepsis

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Summary

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. BM plays an important part in sepsis [6], which contains hematopoietic progenitor cells and supporting niche cells. 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

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