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Gastric ulcers in humans are notoriously chronic and recurring lesions. Although the average individual who undergoes no treatments requires many years for healing, most studies on the healing process of the experimentally induced ulcers have mainly focused on the early stages. Natural history of the ulcer healing has not been completely revealed. We have undertaken long-term investigation up to the 150th day after the cryo-injury to shed light on the natural history of the ulcer healing process compared with developmental changes of postnatal fundic glands. By the 30th day, restitutive gastric glands were mostly seen to cover the ulcer lesions, where well-developed gland-type mucous cells, showing Griffonia simplicifolia agglutinin (GSA)-II labeling, appeared to occupy the basal portion. Most of the bromodeoxyuridine-labeled cells were superimposed on the GSA-II-positive cell zone, forming the proliferative zone. By the 150th day, the restitutive glands were complete, with all epithelial components and topology of the normal fundic glands. The process of the ulcer healing was quite compatible with the developmental changes of the postnatal fundic glands. These results imply that the regeneration of gastric epithelium during the ulcer healing follows pathways linked to the ontogenetic course of the fundic gland. [ABSTRACT FROM AUTHOR]