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Peer-reviewedCC BY-NC-NDStem cell research & therapy

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

  • Steffie Hasevoets1
  • Florian Hermans2
  • Joeri Meyns3,4
  • Hugo Vankelecom5
  • Heidi Declercq6
  • Esther Wolfs2
  • Ivo Lambrichts2
  • Annelies Bronckaers2
6 affiliations
  1. 1Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, 3590, Diepenbeek, Belgium. [email protected].
  2. 2Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, 3590, Diepenbeek, Belgium.
  3. 3Department of Oral and Maxillofacial Surgery, General Hospital St-Jan, Synaps Park 1, 3600, Genk, Belgium.
  4. 4Faculty of Medicine and Life Sciences, LCRC, Hasselt University, 3590, Diepenbeek, Belgium.
  5. 5Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, 3000, Leuven, Belgium.
  6. 6Tissue Engineering Lab, Department of Development and Regeneration, KU Leuven campus KULAK, 8500, Kortrijk, Belgium.
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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 defects of enamel, 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 pharmacological 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 the external exposures investigated can interfere with ameloblast maturation programs in a human-derived in vitro 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 defects of enamel in a human-relevant context.

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Cite

BibTeXRIS
BibTeX
@article{hasevoets2026human,
  title = {{Human epithelial tooth organoids model disrupted amelogenesis following environmental and pharmacological exposures.}},
  author = {Steffie Hasevoets and Florian Hermans and Joeri Meyns and Hugo Vankelecom and Heidi Declercq and Esther Wolfs and Ivo Lambrichts and Annelies Bronckaers},
  journal = {Stem cell research \& therapy},
  year = {2026},
  month = aug,
  doi = {10.1186/s13287-026-05206-y},
  url = {https://europepmc.org/article/MED/42972581},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Human epithelial tooth organoids model disrupted amelogenesis following environmental and pharmacological exposures.
AU  - Steffie Hasevoets
AU  - Florian Hermans
AU  - Joeri Meyns
AU  - Hugo Vankelecom
AU  - Heidi Declercq
AU  - Esther Wolfs
AU  - Ivo Lambrichts
AU  - Annelies Bronckaers
PY  - 2026
DA  - 2026/08/03
JO  - Stem cell research & therapy
DO  - 10.1186/s13287-026-05206-y
UR  - https://europepmc.org/article/MED/42972581
AB  - 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 defects of enamel, 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 pharmacological 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 the external exposures investigated can interfere with ameloblast maturation programs in a human-derived in vitro 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 defects of enamel in a human-relevant context.
SN  - 1757-6512
ER  -