Ameloblasts are the specialized dental epithelial cell type responsible for enamel formation. Following completion of enamel development in humans, ameloblasts are lost and biological repair or regeneration of enamel is not possible. In the past, in vitro models to study dental epithelium and ameloblast biology were limited to freshly isolated primary cells or immortalized cell lines, both with limited translational potential. In recent years, large strides have been made with the development of induced pluripotent stem cell and organoid models of this essential dental lineage – both enabling modeling of human dental epithelium. Upon induction with several different signaling factors (such as transforming growth factor and bone morphogenetic proteins) these models display elevated expression of ameloblast markers and enamel matrix proteins. The advent of 3D bioprinting, and its potential combination with these advanced cellular tools, is poised to revolutionize the field – and its potential for tissue engineering, regenerative and personalized medicine. As the advancements in these technologies are rapidly evolving, we evaluate the current state-of-the-art regarding in vitro cell culture models of dental epithelium and ameloblast lineage with a particular focus toward their applicability for translational tissue engineering and regenerative/personalized medicine.

Graphical Abstract

Future perspectives for in vitro modeling of dental epithelium and ameloblasts. Development of iPSC and organoid models that can reliably generate dental epithelium and ameloblast-like cells, together with advances in 3D bioprinting, provide promising tools for enamel research. Advanced models will provide new avenues for development of enamel repair/regeneration approaches, for testing of dental materials or drugs, studying host-pathogen and/or cell-cell interactions, in vitro modeling of enamel diseases (e.g. amelogenesis imperfecta) and developing novel insights in fundamental tooth biology (e.g. regulation of amelogenesis, lineage specification). Abbreviations: iPSC: induced pluripotent stem cells; TO: tooth organoids; DE: dental epithelium; AB: ameloblast.

中文翻译：

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从多能干细胞到类器官和生物打印：研究牙齿生物学和再生的牙上皮和成釉细胞模型的最新进展

成釉细胞是负责牙釉质形成的特殊牙上皮细胞类型。人类牙釉质发育完成后，成釉细胞就会丢失，牙釉质的生物修复或再生是不可能的。过去，研究牙上皮和成釉细胞生物学的体外模型仅限于新鲜分离的原代细胞或永生化细胞系，两者的转化潜力都有限。近年来，随着诱导多能干细胞和这一重要牙齿谱系的类器官模型的开发取得了长足的进步，两者都能够对人类牙齿上皮进行建模。在用几种不同的信号因子（例如转化生长因子和骨形态发生蛋白）诱导后，这些模型显示成釉细胞标记物和牙釉质基质蛋白的表达升高。3D 生物打印的出现及其与这些先进细胞工具的潜在结合，有望彻底改变该领域及其在组织工程、再生和个性化医学方面的潜力。随着这些技术的进步迅速发展，我们评估了当前关于牙上皮和成釉细胞谱系体外细胞培养模型的最新技术，特别关注它们在转化组织工程和再生/个性化医学中的适用性。

图形概要

牙上皮和成釉细胞体外建模的未来前景。能够可靠地生成牙上皮和成釉细胞样细胞的 iPSC 和类器官模型的开发，加上 3D 生物打印的进步，为牙釉质研究提供了有前途的工具。先进的模型将为开发牙釉质修复/再生方法、测试牙科材料或药物、研究宿主-病原体和/或细胞-细胞相互作用、牙釉质疾病（例如釉质生成不全）的体外建模和开发新见解提供新途径。基础牙齿生物学（例如釉质生成的调节、谱系规范）。缩写：iPSC：诱导多能干细胞；TO：牙齿类器官；DE：牙上皮；AB：成釉细胞。