Abstract
The role of bone marrow-derived mesenchymal stem cells (MSC) in the physiology of the gastrointestinal tract epithelium is currently not well established. These cells can be recruited in response to inflammation due to epithelial damage, home, and participate in tissue repair. In addition, in the case of tissue repair failure, these cells could transform and be at the origin of carcinomas. However, the chemoattractant molecules responsible for MSC recruitment and migration in response to epithelial damage, and particularly to Helicobacter pylori infection, remain unknown although the role of some chemokines has been suggested. This work aimed to get insight into the mechanisms of mouse MSC migration during in vitro infection of mouse gastrointestinal epithelial cells by H. pylori. Using a cell culture insert system, we showed that infection of gastrointestinal epithelial cells by different H. pylori strains is able to stimulate the migration of MSC. This mechanism involves the secretion by infected epithelial cells of multiple cytokines, with a major role of TNFα, mainly via a Nuclear Factor-kappa B-dependent pathway. This study provides the first evidence of the role of H. pylori infection in MSC migration and paves the way to a better understanding of the role of bone marrow-derived stem cells in gastric pathophysiology and carcinogenesis.
Highlights
Almost all tissues possess progenitor cells which can evolve into different specialized cells under physiologic conditions
As none of the bacterial strains was able to stimulate Mesenchymal stem cells (MSC) migration when tested alone, the results suggest that MSC migration was induced in response to chemokines secreted by epithelial cells infected by some strains of H. pylori independently of the type 4 secretion system (T4SS)
MSC have been shown to take part in the gastric carcinogenesis process induced in response to Helicobacter infection, but the molecular mechanisms prompting their recruitment in gastric mucosa still remain unclear [6]
Summary
Almost all tissues possess progenitor cells which can evolve into different specialized cells under physiologic conditions. Bone marrow-derived cells (BMDC) may take part in tissue repair in the case of chronic damage, making them good candidates for regenerative medicine [1]. Concerning the gastrointestinal tract (GIT), engraftment of BMDC can be detected in graft versus host disease or gastric ulcer patients, revealing a close relationship with the course of tissue regeneration [2,3,4]. The mice GIT can be repopulated in relation to the level of damage after local irradiation, as well as in the case of gastritis induced by a chronic bacterial infection [5,6,7,8,9]. MSC have been implicated in wound repair of numerous tissues, and the mechanism of trafficking has become clearer [12]
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