Work

Human epithelial tooth organoids model disrupted amelogenesis following environmental and pharmacological exposures

Year: 2026

Type: article

Abstract: Background Dental enamel formation is a tightly regulated developmental process that is particularly vulnerable to disruption during early life, leading to permanent enamel defects such as molar incisor hypomineralization. While epidemiological studies have linked certain environmental factors and medical treatments to developmental enamel problems, direct causal evidence in humans remains limited due to the lack of suitable in vitro models. Methods Here, we use human epithelial tooth organoids to examine the effects of clinically relevant environmental and therapeutic exposures, including amoxicillin, bisphenol A, vinblastine, and vincristine on ameloblast differentiation and maturation. Organoids were exposed during defined stages of differentiation, followed by gene expression analysis, viability assays, transcriptomic profiling, and ultrastructural characterization. Results Exposure to amoxicillin, vinblastine, and vincristine impaired ameloblast maturation, as evidenced by reduced expression of maturation-stage enamel matrix proteins, including AMTN and ODAM , without markedly affecting overall cell viability or organoid morphology. Transcriptomic analysis of amoxicillin-treated organoids revealed selective downregulation of metabolic and secretory pathways, including oxidative phosphorylation, glycolysis, and unfolded protein response. Furthermore, epithelial tooth organoids recapitulated known mechanisms of action of chemotherapeutic agents, such as α-tubulin depolymerization. These findings indicate that external exposures can directly interfere with ameloblast maturation programs in a human-derived system. Conclusions Our study establishes human epithelial tooth organoids as a robust platform to model exposure-induced disruptions in amelogenesis and provides direct experimental evidence that commonly encountered environmental and pharmacological agents can impair enamel development. This model offers new opportunities to investigate the mechanisms underlying developmental enamel defects and to evaluate potential risk factors in a human-relevant context.

Source: Stem Cell Research & Therapy

DOI: 10.1186/s13287-026-05206-y