Stem-cell-based tissue engineering of murine teeth.
Teeth develop from reciprocal interactions between mesenchyme cells and epithelium, where the epithelium provides the instructive information for initiation. Based on these initial tissue interactions, we have replaced the mesenchyme cells with mesenchyme created by aggregation of cultured non-dental stem cells in mice. Recombinations between non-dental cell-derived mesenchyme and embryonic oral epithelium stimulate an odontogenic response in the stem cells. Embryonic stem cells, neural stem cells, and adult bone-marrow-derived cells all responded by expressing odontogenic genes. Transfer of recombinations into adult renal capsules resulted in the development of tooth structures and associated bone. Moreover, transfer of embryonic tooth primordia into the adult jaw resulted in development of tooth structures, showing that an embryonic primordium can develop in its adult environment. These results thus provide a significant advance toward the creation of artificial embryonic tooth primordia from cultured cells that can be used to replace missing teeth following transplantation into the adult mouth.
Ohazama
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Department of Craniofacial Development, Floor 28, GKT Dental Institute, King's College, Guy's Hospital, London Bridge, London SE1 9RT, UK.
Modino
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SA
Miletich
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Sharpe
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PT
D016475:3T3 Cells; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D018920:Coculture Techniques / Q000379:methods; D004627:Embryonic Induction; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D051957:MSX1 Transcription Factor; D008334:Mandible / Q000166:cytology / Q000196:embryology; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009055:Mouth / Q000166:cytology; D039902:Multipotent Stem Cells / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology; D009805:Odontogenesis / Q000502:physiology*; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; D023822:Tissue Engineering / Q000379:methods*; D014070:Tooth / Q000254:growth & development* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D018398:Homeodomain Proteins; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D051957:MSX1 Transcription Factor; D051764:PAX9 Transcription Factor; D051761:Paired Box Transcription Factors; C488759:Pax9 protein, mouse; D014157:Transcription Factors