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Efficient induction of functional ameloblasts from human keratinocyte stem cells.

Xuefeng Hu1,2, Jyh-Wei Lee3,4,5, Xi Zheng2

  • 1Southern Center for Biomedical Research, Fujian Normal University, Fuzhou, 350108, China.

Stem Cell Research & Therapy
|May 4, 2018
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Fibroblast growth factor 8 (FGF8) and Sonic hedgehog (SHH) treatments enhanced human keratinocyte stem cell (hKSC) stemness, significantly improving tooth-like structure formation and ameloblastic differentiation in human-mouse chimeric tooth germs.

Keywords:
AmeloblastEnamelFibroblast growth factor 8Keratinocyte stem cellsSonic hedgehog

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Regenerative medicine

Background:

  • Adult human epidermal stem cells can regenerate enamel but with low efficiency.
  • Further investigation is needed on the structural and mechanical properties of regenerated enamel.

Purpose of the Study:

  • To investigate the effect of FGF8 and SHH on human keratinocyte stem cells (hKSCs) for enhanced tooth regeneration.
  • To analyze the structural and mechanical properties of the regenerated enamel.

Main Methods:

  • hKSCs were treated with FGF8 and SHH, then recombined with mouse dental mesenchyme to form chimeric tooth germs.
  • Recombinant tooth germs were cultured in nude mice and analyzed using histological, immunohistochemical, and mechanical testing methods.
  • Scanning electron microscopy evaluated enamel prism patterns, and nanoindentation assessed mechanical properties.

Main Results:

  • FGF8 and SHH treatment increased tooth-like structure formation to approximately 70%.
  • These growth factors enhanced hKSC stemness and ameloblastic differentiation.
  • Regenerated enamel showed prism patterns similar to human enamel, with mechanical properties improving over time.

Conclusions:

  • FGF8 and SHH application enhances hKSC stemness and ameloblastic differentiation efficiency.
  • This leads to improved tooth formation in human-mouse chimeric tooth germs.
  • While not directly inducing odontogenic fate, these factors significantly boost regenerative potential.