Stem Cells in the Face: Tooth Regeneration and Beyond

Mao, Jeremy J.; Prockop, Darwin J.

doi:10.1016/j.stem.2012.08.010

Cited by 104 publications

(96 citation statements)

References 114 publications

(120 reference statements)

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“…First, our ectopic transplantation model with Lhx8 over-expressed dental pulp stem/progenitor cells is perhaps not nearly as instructive for tooth regeneration as an orthotopic model with native dentin as a substrate. Second, adult dental pulp stem/progenitor cells are highly heterogeneous [44] and even with Lhx8 overexpression likely do not overwhelmingly transform into odontoblasts with the capacity as E14.5 dental mesenchyme cells for dentinogenesis. Third, Lhx8 overexpressed dental pulp stem/progenitor cells are in an artificial state and their RNASeq comparison with cells of the same population should be considered accordingly.…”

Section: Discussionmentioning

confidence: 99%

“…Decoding the molecular network of Lhx8 appears to be crucial for our understanding of not only tooth development, but also tooth regeneration. E14.5 dental mesenchyme cells have the ability to induce tooth morphogenesis, when combined with non-dental epithelium[19, 41–44]. Lhx8 appears to maintain dental mesenchymal cells in an undifferentiated stage via Wnt and TGFβ pathways, and thus may be crucial in retaining the induction capacity of dental mesenchyme.…”

Section: Discussionmentioning

confidence: 99%

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Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration

et al. 2015

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LIM homeobox 8 (Lhx8) is a highly conserved transcriptional factor with recently illustrated roles in cholinergic and GABAergic differentiation, and is expressed in neural crest derived craniofacial tissues during development. However, Lhx8 functions and signaling pathways are largely elusive. Here we showed that Lhx8 regulates dental mesenchyme differentiation and function via Wnt and TGFβ pathways. Lhx8 expression was restricted to dental mesenchyme from E11.5 to a peak at E14.5, and absent in dental epithelium. By reconstituting dental epithelium and mesenchyme in an E16.5 tooth organ, Lhx8 knockdown accelerated dental mesenchyme differentiation; conversely, Lhx8 overexpression attenuated dentin formation. Lhx8 overexpressed adult human dental pulp stem/progenitor cells in β-tricalcium phosphate cubes attenuated mineralized matrix production in vivo. Gene profiling revealed that postnatal dental pulp stem/progenitor cells upon Lhx8 overexpression modified several matrix related gene expression including Dspp, Cola1 and osteocalcin. Lhx8 transcriptionally activates Wnt and TGFβ pathways, and its attenuation upregulates multiple dentinogenesis genes. Together, Lhx8 regulates dentin development and regeneration by fine-turning Wnt and TGFβ signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration

et al. 2015

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“…Cell source is a central impediment for tooth regeneration in patients and has stimulated numerous investigations [6]. Mouse embryonic tooth germ cells, specifically E10 dental epithelium or E14.5 mouse dental mesenchyme, can clearly initiate tooth morphogenesis [6].…”

Section: Introductionmentioning

confidence: 99%

“…Mouse embryonic tooth germ cells, specifically E10 dental epithelium or E14.5 mouse dental mesenchyme, can clearly initiate tooth morphogenesis [6]. Mouse E14.5 dental mesenchyme, when combined with oral epithelium of toothless chicks, gave rise to a developing tooth organ [7].…”

Section: Introductionmentioning

confidence: 99%

Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis

et al. 2014

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Rodent incisors provide a classic model for studying epithelial-mesenchymal interactions in development. However, postnatal stem/progenitor cells in rodent incisors have not been exploited for tooth regeneration. Here, we characterized postnatal rat incisor epithelium and mesenchyme stem/progenitor cells and found that they formed enamel- and dentin-like tissues in vivo. Epithelium and mesenchyme cells were harvested separately from the apical region of postnatal 4–5 day rat incisors. Epithelial and mesenchymal phenotypes were confirmed by immunocytochemistry, CFU assay and/or multi-lineage differentiation. CK14+, Sox2+ and Lgr5+ epithelium stem cells from the cervical loop significantly enhanced amelogenin and ameloblastin expression upon BMP4 or FGF3 stimulation, signifying their differentiation towards ameloblast-like cells, whereas mesenchyme stem/progenitor cells upon BMP4, BMP7 and Wnt3a treatment robustly expressed Dspp, a hallmark of odontoblastic differentiation. We then control-released microencapsulated BMP4, BMP7 and Wnt3a in transplants of epithelium and mesenchyme stem/progenitor cells in the renal capsule of athymic mice in vivo. Enamel and dentin-like tissues were generated in two integrated layers with specific expression of amelogenin and ameloblastin in the newly formed, de novo enamel-like tissue, and DSP in dentin-like tissue. These findings suggest that postnatal epithelium and mesenchyme stem/progenitor cells can be primed by pivotal signals towards bioengineered tooth regeneration.

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“…This information can be applied experimentally in in vitro assays for regenerating teeth, hair, or feathers, which involve the assembly of induced pluripotent stem cells or ESCs. 12,[15][16][17][18][19] Similar state-of-the-art bioengineering methods have been developed to generate in vitro skin appendages by assembling single cells from both the embryonic epithelium and mesenchyme and then combining the epithelium and mesenchyme as a bilayer. Teeth, 10,20,21 hair, [22][23][24] and feathers 25 have been successfully generated with a nearly uniform size on such reconstructed bilayers, which are referred to as bioengineered skin.…”

Section: 2mentioning

confidence: 99%

Role of the boundary in feather bud formation on one-dimensional bioengineered skin

Ishida

Mitsui

2018

APL Bioengineering

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The role of a boundary in pattern formation from a homogenous state in Turing's reaction–diffusion equations is important, particularly when the domain size is comparable to the pattern scale. Such experimental conditions may be achieved for in vitro regeneration of ectodermal appendages such as feathers, via reconstruction of embryonic single cells. This procedure can eliminate a predefined genetic map, such as the midline of chick feather bud formation, leaving uniformly distributed identical cells as a bioengineered skin. Here, the self-organizing nature of multiple feather bud formation was examined in bioengineered 1D-skin samples. Primal formation of feather buds occurred at a fixed length from the skin edge. This formation was numerically recapitulated by a standard two-component reaction-diffusion model, suggesting that the boundary effect caused this observation. The proper boundary conditions were nonstandard, either mixed Dirichlet–Neumann or partial-flux. In addition, the model implies imperfect or hindered bud formation as well as nearly equal distances between buds. In contrast, experimental observations indicated that the skin curvature, which was not included in our model, also strongly affected bud formation. Thus, bioengineered skin may provide an ideal template for modeling a self-organized process from a homogenous state. This study will examine the possible diffusion activities of activator or inhibitor molecular candidates and mechanical activities during cell aggregation, which will advance our understanding of skin appendage regeneration from pluripotent or embryonic stem cells.

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Stem Cells in the Face: Tooth Regeneration and Beyond

Cited by 104 publications

References 114 publications

Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration

Lhx8 mediated Wnt and TGFβ pathways in tooth development and regeneration

Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis

Role of the boundary in feather bud formation on one-dimensional bioengineered skin

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