State Key Laboratory of Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Dent Res. 2021 May;100(5):454-463. doi: 10.1177/0022034520983808. Epub 2021 Jan 21.
Oral organoids are complex 3-dimensional structures that develop from stem cells or organ-specific progenitors through a process of self-organization and re-create architectures and functionalities similar to in vivo organs and tissues in the oral and maxillofacial region. Recently, striking advancements have been made in the construction and application of oral organoids of the tooth, salivary gland, and tongue. Dental epithelial and mesenchymal cells isolated from tooth germs or derived from pluripotent stem cells could generate tooth germ-like organoids by self-organization in a specific culture system. Tooth organoids can also be constructed based on tissue engineering principles by seeding stem cells on a scaffold with the bioregulatory functions of odontogenic differentiation. Two main approaches have been used to construct salivary gland organoids: 1) incubation of salivary gland-derived stem/progenitor cells in a 3-dimensional culture system to form the structure of the gland through mimicking regenerative processes and 2) inducing of pluripotent stem cells to generate embryonic salivary glands by replicating the development process. Taste bud organoids can be generated by embedding isolated circumvallate papilla tissue in Matrigel with a mixture of growth factors, while lingual epithelial organoids have been constructed using lingual stem cells in a suitable culture system containing specific signaling molecules. These oral organoids usually maintain the main functions and characteristic structures of the corresponding organ to a certain extent. Furthermore, using cells isolated from patients, oral organoids could replicate specific diseases such as maxillofacial tumors and tooth dysplasia. Until now, oral organoids have been applied in the study of mechanisms of tooth development, pathology and regeneration of the salivary gland, and precision therapeutics for tongue cancer. These findings strongly demonstrate that the organoid technique is a novel paradigm for the study of the development, pathology, and regeneration of oral and maxillofacial tissue.
口腔类器官是复杂的三维结构，通过自组织过程从干细胞或器官特异性祖细胞发育而来，可重建与口腔和颌面区域体内器官和组织相似的结构和功能。最近，在构建和应用牙齿、唾液腺和舌的口腔类器官方面取得了显著进展。从牙胚中分离出的牙上皮和间充质细胞或来源于多能干细胞，可在特定的培养系统中通过自组织生成类牙胚样类器官。基于组织工程原理，通过将干细胞接种在具有牙向分化生物调节功能的支架上，也可以构建牙齿类器官。构建唾液腺类器官主要有两种方法：1）在三维培养系统中孵育唾液腺来源的干细胞/祖细胞，通过模拟再生过程形成腺体结构；2）通过复制发育过程，诱导多能干细胞生成胚胎唾液腺。将分离的环状乳头组织嵌入含有生长因子的 Matrigel 中可以生成味蕾类器官，而使用含有特定信号分子的合适培养系统中的舌干细胞则可以构建舌上皮类器官。这些口腔类器官通常在一定程度上保持相应器官的主要功能和特征结构。此外，使用从患者中分离的细胞，口腔类器官可以复制特定疾病，如颌面肿瘤和牙齿发育不良。到目前为止，口腔类器官已应用于牙齿发育、唾液腺病理学和再生以及舌癌精准治疗的研究。这些发现有力地证明了类器官技术是研究口腔颌面组织发育、病理学和再生的一种新范例。
