7 Mouse studies have proposed several markers for gastric stem cells.4, 8, 9, 10 and 11 Two markers, Lgr5 and Troy, have allowed the identification of cells that have the capacity to self-renew and to generate the different lineages of the stomach in vivo.4 and 11 Research on human gastric stem cells currently is limited. The analysis of spontaneous mutations in the cytochrome c oxidase gene has shown that some, but not all, human gastric units are monoclonal, allowing the conclusion that at

one point in life multipotent stem cells have resided in these units.3 However, direct evidence for the presence PD-166866 cost of multipotent gastric stem cells into adulthood is lacking. One of the http://www.selleckchem.com/products/ganetespib-sta-9090.html major functions of the gastrointestinal epithelium is to shield the body from infections and to maintain a peaceful co-existence with the gut commensals. Studies on host–pathogen or host–commensal interactions rely on the use of established model systems such as infection of animals or cancer cell lines,12 but for many pathogens

and commensals, such model systems have not been established yet. The gastric pathogen Helicobacter pylori is one of the most successful pathogens. It uses a range of biological strategies to ensure persistency, which enables it to colonize the stomach of about half of the world’s population. 13 Chronic infection can cause gastric ulcers and gastric cancer. 13 Currently, in vivo experimental studies use rodent models to understand H pylori infection. Although mouse studies certainly are useful, the clinical outcome of infection in mice is usually a mild gastritis that does not progress to ulceration or cancer. Alternatively, the Mongolian gerbil can develop cancer after H pylori infection, but these animals are outbred and the study of host factors therefore would be limited. 12 Other studies use gastric cancer cell lines that typically harbor oncogenic

mutations. Human primary cells would represent the gastric epithelium much more closely, but current techniques are limited to isolation of differentiated (mostly mucous) cells that are not able to self-renew and thus can be maintained for only a few days. 14, 15 and 16 No expanding primary gastric culture system exists that enables during research of primary human gastric cells. Here, we present a gastric culture system that allows indefinite (>1 y) expansion of human gastric cells. The cultures differentiate into the gastric lineages and can be used as a tool to study stem cell biology as well as the response of the epithelium to infection. Human corpus tissue was obtained from 17 patients (12 men, 5 women; age range, 41–87 y) who underwent partial or total gastrectomy at the University Medical Centre Utrecht. Ten patients were diagnosed with gastric cancer and 7 patients were diagnosed with esophageal cancer.