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Biomaterials. 2014 Feb;35(7):2172-80. doi: 10.1016/j.biomaterials.2013.11.061. Epub 2013 Dec 15.

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

Author information

1
Department of Orthodontics, Peking University School & Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China; Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
2
Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
3
Department of Orthodontics, Peking University School & Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
4
Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA. Electronic address: jmao@columbia.edu.

Abstract

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 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 towards bioengineered tooth regeneration.

KEYWORDS:

BMP; Epithelial; Mesenchymal; Stem cells; Tooth regeneration; Wnt

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