Adult dental epithelial stem cell-derived organoids deposit hydroxylapatite biomineral

IF 10.8 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-12-07 DOI:10.1038/s41368-023-00257-w

Hyun-Yi Kim, Victoria Cooley, Eun-Jung Kim, Shujin Li, Jong-Min Lee, Dina Sheyfer, Wenjun Liu, Ophir D. Klein, Derk Joester, Han-Sung Jung

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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.

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成人牙齿上皮干细胞衍生的器官组织沉积羟基磷灰石生物矿物质

釉母细胞是源自牙齿上皮的特化细胞，可产生釉质，釉质是一种由高度拉长的羟基磷灰石（OHAp）结晶体组成的分层结构组织。上皮细胞合成结晶并将其组装成机械坚固结构的独特功能尚未完全阐明，部分原因是体外实验模型的局限性。在此，我们证明了从小鼠门牙组织中分离出的成牙上皮干细胞（aDESCs）生成矿化牙上皮器官组织（DEOs）的能力。DEOs表达成釉细胞标记，可在含有Wnt、Egf、Bmp、Fgf和Notch信号通路调节剂的培养基中体外维持5个月（11次传代）以上，并适合低温保存。当移植到小鼠肾囊下时，器官组织产生的OHAp结晶在成分、大小和形状上与矿化牙齿组织相似，包括一些类似珐琅质的细长结晶。因此，DEOs是研究牙齿上皮矿化过程的强大体外模型，可为了解釉质形成和开发釉质再生疗法铺平道路。

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来源期刊

International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-

CiteScore

31.80

自引率

1.30%

发文量

审稿时长

>12 weeks

期刊介绍： The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.