Helicobacter. 2018;e12489. wileyonlinelibrary.com/journal/hel
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https://doi.org/10.1111/hel.12489
© 2018 John Wiley & Sons Ltd
DOI: 10.1111/hel.12489
ORIGINAL ARTICLE
A simple and cost-efficient adherent culture platform
for human gastric primary cells, as an in vitro model for
Helicobacter pylori infection
Samaneh Saberi
1
| Behshad Pournasr
2
| Zahra Farzaneh
2
| Maryam Esmaeili
1
|
Mahmoud Eshagh Hosseini
3
| Hossein Baharvand
2,4
| Marjan Mohammadi
1
1
HPGC Research Group, Department of
Medical Biotechnology, Pasteur Institute of
Iran, Tehran, Iran
2
Department of Stem Cells and
Developmental Biology, Cell Science
Research Center, Royan Institute for Stem
Cell Biology and Technology, ACECR,
Tehran, Iran
3
Gastroenterology Department, Amiralam
Hospital, Tehran University of Medical
Sciences, Tehran, Iran
4
Department of Developmental
Biology, University of Science and Culture,
Tehran, Iran
Correspondence
Marjan Mohammadi, HPGC Research Group,
Department of Medical Biotechnology,
Pasteur Institute of Iran, Tehran, Iran.
Email: marjan.mohammadi@pasteur.ac.ir
and
Hossein Baharvand, Department of Stem
Cells and Developmental Biology, Cell
Science Research Center, Royan Institute for
Stem Cell Biology and Technology, ACECR,
Tehran, Iran.
Email: baharvand@royaninstitute.org
Funding information
Pasteur Institute of Iran: Grant/Award
Number: #722; and #TP-9121 and Royan
Institute: Grant/Award Number: 94000090
Abstract
Background: Most two- dimensional in vitro models for studying host- H. pylori inter-
actions rely on tumor-derived cell lines, which harbor malignant alterations. The re-
cent development of human gastric organoids has overcome this limitation and
provides a highly sophisticated, yet costly, short-term model for H. pylori infection,
with restricted use in low-budget centers.
Method: Tissue specimens from upper, middle, and lower stomachs of H. pylori-
negative volunteers were collectively dispersed and cultured on mouse embryonic
fibroblast (MEF) or collagen-coated plates. Gastric primary cells (GPCs) were evalu-
ated by light microscopy, immunostaining, qRT-PCR and ELISA analysis of cellular
secretions, before and after H. pylori infection.
Results: The formation and long-term (up to 1 year) maintenance of GPCs was highly
dependent on adherent inactivated MEF cells, cultured in enriched media. These cells
were multipassageable and able to undergo stable freezer storage and subsequent
revival. The cellular composition of GPCs included the combination of cytokeratin 18
(CK18) and E-cadherin (E-cad)-positive epithelial cells, MUC5AC-positive gastric cells,
and leucine-rich repeat containing G protein-coupled receptor 5 (LGR5)-positive pro-
genitor cells. These cells produced significant amounts of gastric pepsinogens I and II.
GPCs also allowed for extended (up to 96 hours) H. pylori infection, during which they
underwent morphological alterations (cellular vacuolation and elongation) and hyper-
production of gastric pepsinogens and inflammatory cytokines (IL-8 and TNF- α).
Conclusion: We, hereby, present a simple, consistent, and cost-efficient gastric cell
culture system, which provides a suitable model for extended in vitro infection of
H. pylori. This platform can be employed for a variety of gastric-related research.
KEYWORDS
epithelial, gastric, Helicobacter pylori, human, primary, progenitor
1 | INTRODUCTION
The gastric lumen, in the gastrointestinal tract, remains a se-
cluded entity, which has made its study difficult for interested
investigators. On the other hand, the mere fact that a previously
believed sterile environment can become colonized with a carcino-
genic pathogen (Helicobacter pylori ), has attracted extensive inter-
est in studying the real-time molecular details of its host-pathogen