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Abstract
Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.
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1 NGeneS Inc., Ansan-si, Korea
2 Northwestern University, Department of Materials Science and Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Advanced Photon Source, Argonne National Laboratory, X-ray Science Division, Lemont, USA (GRID:grid.187073.a) (ISNI:0000 0001 1939 4845)
3 Yonsei University College of Dentistry, Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 FOUR Project, Seoul, Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
4 Advanced Photon Source, Argonne National Laboratory, X-ray Science Division, Lemont, USA (GRID:grid.187073.a) (ISNI:0000 0001 1939 4845)
5 University of California, Department of Orofacial Sciences and Program in Craniofacial Biology, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811); Cedars-Sinai Guerin Children’s, Department of Pediatrics, Los Angeles, USA (GRID:grid.266102.1)
6 Northwestern University, Department of Materials Science and Engineering, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507)