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. 1999 Apr;67(4):1798-805.
doi: 10.1128/IAI.67.4.1798-1805.1999.

Human embryonic gastric xenografts in nude mice: a new model of Helicobacter pylori infection

A Lozniewski  1 , F Muhale, R Hatier, A Marais, M C Conroy, D Edert, A le Faou, M Weber, A Duprez
Affiliations

Human embryonic gastric xenografts in nude mice: a new model of Helicobacter pylori infection

A Lozniewski et al. Infect Immun. 1999 Apr.

Abstract

In vitro or animal models have been used to investigate the pathogenesis of Helicobacter pylori infection. However, extrapolation to humans of results obtained with these heterologous models remains difficult. We have developed a new model for the study of H. pylori infection that uses human entire embryonic stomachs engrafted in nude mice. At 80 days after implantation, 22 of these xenografts, which exhibited a mature gastric epithelium, were inoculated with 10(7) to 10(8) CFU of either H. pylori LB1, a freshly isolated H. pylori strain (n = 12), or H. pylori ATCC 49503 (n = 10). After 12-week examination, H. pylori LB1 persistently colonized the antrum of all inoculated grafts, as assessed by culture (mucus and mucosa), immunohistochemistry (mucosa), and a rapid urease test (mucus). H. pylori ATCC 49503, either before or after in vivo passage, permitted only a transient 2-week colonization in one of the five inoculated grafts in both groups. Colonization was always associated with an increase of gastric juice pH. A mild neutrophil infiltration of the gastric mucosa was noted solely in infected grafts. Transmission electron microscopy showed adherence of H. pylori organisms to epithelial cell surface. In six animals, intracytoplasmic location of this bacterium was observed in the antrum or the fundus. These results allow us to propose this model as a new ex vivo model for the study of specific H. pylori-gastric cell interactions.

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Figures

FIG. 1
FIG. 1
Graft implantation and catheterization. (A) Entire embryonic stomach of 8 weeks of gestational age. Bar = 1 mm. (B) Just engrafted stomach (st) with esophagus (small arrow) stitched to the peritoneum (p) and in close contact with the epigatric vessels (large arrow). (C) Xenograft exposed after incision of the abdominal skin (3 months after engraftment). Bar = 5 mm. (D) Catheter (small arrow) implanted in a mature xenograft (large arrow). (E) Nude mice with a catheter (small arrow) coming out at the nape of the neck. A tumefaction corresponding to the xenograft is visible on the right flank (large arrow).
FIG. 2
FIG. 2
Hematoxylin-and-eosin-stained sections of human gastric mucosa from uninfected and infected xenografts at 12 weeks after inoculation with H. pylori LB1. (A and B) Normal gastric antral mucosa. (C and D) Gastric infected mucosa, showing dilated capillaries (arrows) and mild infiltration of mononuclear cells and rare polymorphonuclear leukocytes (∗). Bars = 50 μm.
FIG. 3
FIG. 3
H. pylori bacteria at the surface of mucus cells in the gastric antral mucosa from an infected xenograft (immunohistochemical peroxidase staining). Bar = 10 μm.
FIG. 4
FIG. 4
Transmission electron micrograph showing the attachment of H. pylori organisms to the surface of gastric epithelial cells with filamentous strands between bacterial membrane and cytoplasmic membrane (arrows). Bar = 0.25 μm.
FIG. 5
FIG. 5
Transmission electron micrograph showing H. pylori organism (arrow) in the canalicular system of a parietal cell. Bar = 0.5 μm.
FIG. 6
FIG. 6
Transmission electron micrograph showing cross-sectioned H. pylori with sectioned flagella in the cytoplasm of a parietal cell. Bar = 0.5 μm.
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