NGeneS Inc., Ansan-si, Gyeonggi-do, Korea.
Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
Int J Oral Sci. 2023 Dec 7;15(1):55. doi: 10.1038/s41368-023-00257-w.
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.
成釉细胞是一种来源于牙上皮的特化细胞,能够产生釉质,这是一种具有层次结构的组织,由高度拉长的羟基磷灰石(OHAp)微晶组成。合成微晶并将其组装成机械坚固结构的上皮细胞的独特功能尚未完全阐明,部分原因是体外实验模型存在局限性。在此,我们展示了从成年牙齿上皮干细胞(aDESCs)中分离出的小鼠切牙组织中生成矿化牙齿上皮类器官(DEO)的能力。DEO 表达成釉细胞标志物,在含有 Wnt、Egf、Bmp、Fgf 和 Notch 信号通路调节剂的培养基中,可在体外维持超过五个月(11 代),并且易于进行冷冻储存。当移植到小鼠肾囊下时,类器官产生的 OHAp 微晶在组成、大小和形状上与矿化牙齿组织相似,包括一些类似牙釉质的拉长晶体。因此,DEO 是研究牙齿上皮矿化过程的强大体外模型,这可以为理解牙发生和开发牙釉质再生疗法铺平道路。
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