Helicobacter pylori Infection Recruits Bone Marrow−Derived Cells That Participate in Gastric Preneoplasia in Mice

Background & Aims

Studies in animal models have shown that bone marrow−derived cells (BMDC) could be involved in the formation of carcinomas of the upper gastrointestinal tract, including gastric carcinoma. Most gastric carcinomas in humans have been associated with chronic infection with Helicobacter pylori; we investigated the bacteria's potential to induce premalignant lesions in mice and studied the kinetics of BMDC settlement in the gastric epithelium.

Methods

C57BL/6J female chimeric mice with BMDCs from male donors that express green fluorescent protein were infected with human-derived and mouse-adapted strains of H pylori and followed. We assessed development of pathologic features and recruitment of BMDC to the gastric mucosa using immunohistochemistry and fluorescent in situ hybridization analyses of gastric tissue sections.

Results

Infection of mice with different strains of H pylori led to the development of chronic inflammation, hyperplasia, and mucinous metaplasia, and, later in life, of pseudointestinal metaplasia and dysplasia. After 1 year, gastric glands that contained green fluorescent protein−positive male cells were detected in 50%−90% of female chimeric mice infected with H pylori strains; the presence of these glands correlated with the development of pseudointestinal metaplasia. Twenty-two percent of H pylori−induced dysplastic lesions were composed of glands that contained epithelial BMDCs.

Conclusions

H pylori infection leads to development of chronic inflammation, hyperplasia, metaplasia, and dysplasia, as well as the recruitment and accumulation of BMDC in the gastric epithelial mucosa. Nearly 25% of dysplastic lesions include cells that originate from the BM.

Keywords:  Gastro-Intraepithelial Neoplasia , Stem Cell , Spasmolytic Polypeptide Expressing Metaplasia , Cag Pathogenicity Island

Abbreviations used in this paper:  BM, bone marrow, BMDC, bone marrow−derived cell, CSC, cancer stem cell, GFP, green fluorescent protein, GIN, gastro-intraepithelial neoplasia, MSC, mesenchymal stem cell, WPI, weeks post-infection, WT, wild-type