title: Postnatal epithelium and mesenchyme stem/progenitor cells in bioengineered amelogenesis and dentinogenesis.
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.
authors.affiliation: 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.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
authors.forename: Mo
authors.initials: M
authors.lastname: Chen
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schiff
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
authors.forename: Chang H
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
authors.forename: Kimi
authors.initials: K
authors.lastname: Kong
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA.
authors.forename: Mildred C
authors.initials: MC
authors.lastname: Embree
authors.affiliation: Department of Orthodontics, Peking University School & Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
authors.forename: Yanheng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Columbia University Medical Center, Center for Craniofacial Regeneration (CCR), 630 W. 168 St. - PH7E, New York, NY 10032, USA. Electronic address: jmao@columbia.edu.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Mao
mesh_terms: D000566:Amelogenesis; D000818:Animals; D003810:Dentinogenesis; D004847:Epithelial Cells / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
keywords: BMP; Epithelial; Mesenchymal; Stem cells; Tooth regeneration; Wnt