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.
| Original language | English (US) |
|---|---|
| Article number | 55 |
| Journal | International Journal of Oral Science |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Funding
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) (NRF-2022R1A2B5B03001627). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. This work made use of the following core facilities operated by Northwestern University: EPIC and SPID facilities of Northwestern University\u2019s NUANCE Center, which have received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern\u2019s MRSEC program (NSF DMR-1720139); MatCI, supported by the MRSEC program (NSF DMR-1720139) at the Materials Research Center; and the Northwestern University George M. O\u2019Brien Kidney Research Core Center (NU GoKidney), an NIH/NIDDK funded program (P30DK114857). V.C., D.J. and O.D.K. were supported in part by NIH UH3 DE028872. V.C. was supported in part by the National Science Foundation through a Graduate Research Fellowship (DGE-1842165). The authors thank Dr. R. Free for contributing custom code for data analysis, Prof. S. R. Stock (Northwestern) for aid in analyzing \u00B5XRD data, and Prof. N. Blair (Northwestern) for assistance in acquiring \u03BCIR data.
ASJC Scopus subject areas
- General Dentistry