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The purpose of this study was to ascertain the regenerative characteristics of apical papilla–derived cells (APDCs) from immature teeth with pulpal and periapical pathosis and thus to provide proof-of-principle evidence for further regenerative endodontic research.Pulpal and periapical pathosis was induced in immature permanent double-rooted premolars of beagles, which were randomly assigned to experimental treatment groups: group AO (n = 14), pulp disruption and access left open; group PS (n = 14), supragingival plaque suspension-soaked cotton pellet was introduced, and access was sealed; and control (n = 7), untreated. The teeth were extracted at 2- and 4-week periods after experimental treatments. APDCs were cultured from the extracted teeth, and their cellular proliferation, differentiation characteristics, and stemness were assessed. The data were statistically analyzed.After 4 weeks of intentional pulpal and periapical pathosis induction period, all teeth in group PS showed features of apical periodontitis with necrotic pulp, and their APDCs showed significantly increased proliferation rate and osteogenic/odontogenic differentiation capabilities (P < .05). The stemness was maintained in all APDCs, although the stem cell population was smaller in group PS at 2-week period when the inflammatory responses were most fulminant (P < .05).The APDCs from immature teeth retained the regenerative characteristics with the differences according to their pulpal and periapical pathosis. The results of this study partly provide the evidence for regenerative endodontic research.Regenerative characteristics of inflamed apical papilla–derived cells (APDCs) were investigated.Features of apical periodontitis with necrotic pulp were induced in beagle immature teeth.The APDCs retained the regenerative characteristics and stemness regardless of the inflammatory status.