Acid secretion and response to pentagastrin or omeprazole in human fetal stomach xenografts

Background: The dual capacity of stomach tissue to secrete acid and to resp ond to secretagogues is indicative of the terminal stages of gastric functi onal maturation. In this study 6- to 10-week-old human fetal stomachs xenog rafted into nude mice were used to study parietal cells' functional maturat ion. Methods: Thirty-four transplants were microsurgically grafted either inside a pouch created on the nude peritoneum(n = 15) or on the host stomach and esophagus (n = 19). The mucosa of transplanted tissues was analyzed by immu nohistochemical techniques to detect gastric cells. Gastric cell secretions were collected before and after pentagastrin or omeprazole treatment. Results: Parietal, G, and D cells were detected immunohistochemically only after 1 month of grafting. All xenografts actively secreted acid after 1 or 2 months' transplantation at each graft site. Acid secretion was significa ntly stimulated by intraperitoneally injected pentagastrin (mean pH +/- SD, 3.2 +/- 0.7 vs. 2.0 +/- 0.5; n = 10, P = 0.005) and was dramatically inhib ited by intragastrically administered omeprazole (2.3 +/- 0.6 vs. 6.5 +/- 0 .7; n = 15, P = 0.0007) after 5 hours. Conclusion: Stomach xenografts were able to develop normally. Parietal cell s were physiologically mature with functional proton pumps and active gastr in receptors, as demonstrated after omeprazole and pentagastrin treatment, respectively. Because stomach xenografts matured very rapidly, it is possib le that a stomach xenograft model can be used for further studies on the fu nctional maturation of human gastric epithelial cells, as well as the facto rs that influence this maturation in humans. (C) 2000 Lippincott Williams & Wilkins, Inc.