Organoids from human tooth showing epithelial stemness phenotype and differentiation potential

Area of Science:

• Stem Cell Biology
• Developmental Biology
• Regenerative Medicine

Background:

• Human tooth epithelial stem cell biology is poorly understood.
• Tissue-derived organoid models are crucial for studying epithelial stem cell compartments.
• Dental follicle tissue contains dental epithelial stem cells.

Purpose of the Study:

• To develop a novel epithelial organoid model from human tooth dental follicle tissue.
• To investigate human tooth epithelial stem cell phenotype, function, and interactions.
• To explore potential applications in tooth regeneration.

Main Methods:

• Dental follicle tissue isolation from unerupted wisdom teeth.
• Generation and long-term expansion of epithelial organoids.
• Single-cell transcriptomics for phenotype analysis.
• Stimulation with epidermal growth factor (EGF) and transforming growth factor-beta (TGFβ).
• Development of mesenchymal-epithelial composite organoid (assembloid) models.

Main Results:

• Epithelial organoids exhibited stemness phenotype congruent with epithelial cell rests of Malassez (ERM).
• Organoids mirrored novel stem cell features and responded to EGF with proliferation and epithelial-mesenchymal transition.
• Organoids underwent ameloblast differentiation, modulated by TGFβ signaling.
• Mesenchymal-epithelial composite organoids demonstrated the importance of mesenchyme-epithelium interaction in differentiation.

Conclusions:

• Novel human tooth epithelial stem cell organoid models have been successfully developed.
• These models enable exploration of stem cell biology, function, and mesenchymal interactions.
• The models provide a platform for advancing tooth regeneration strategies.