Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral

被引:9
作者
Kim, Hyun-Yi [1 ]
Cooley, Victoria [2 ,3 ]
Kim, Eun-Jung [4 ]
Li, Shujin [4 ]
Lee, Jong-Min [4 ]
Sheyfer, Dina [3 ]
Liu, Wenjun [3 ]
Klein, Ophir D. [5 ,6 ,7 ]
Joester, Derk [2 ]
Jung, Han-Sung [4 ]
机构
[1] Insilicogen Inc, Suwon, Gyeonggi Do, South Korea
[2] Northwestern Univ, Dept Mat Sci & Engn, Evanston, IL USA
[3] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Lemont, IL USA
[4] Yonsei Univ, BK21 FOUR Project, Oral Sci Res Ctr, Dept Oral Biol,Coll Dent,Div Anat & Dev Biol, Seoul, South Korea
[5] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA USA
[6] Univ Calif San Francisco, Program Craniofacial Biol, San Francisco, CA USA
[7] Cedars Sinai Guerin Childrens, Dept Pediat, Los Angeles, CA USA
基金
新加坡国家研究基金会; 美国国家科学基金会;
关键词
TOOTH; NOTCH; TISSUE; MOLAR; PROLIFERATION; MORPHOGENESIS; INHIBITION; EXPRESSION; CADHERIN; SPECTRA;
D O I
10.1038/s41368-023-00257-w
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
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.
引用
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页数:15
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