journal article·2025-01Open access

A Chemically Defined Culture for Tooth Reconstitution

Ziwei Zhang, Hong Hu, Zhiheng Xu, Ce Shan, Hanyi Chen, Kun Xie, Kun Wang, Yifu Wang, Qing Zhu, Yike Yin, Haoyang Cai, Yunqiu Zhang, Zhonghan Li

Advanced Science· Volume 12· Issue 3

Abstract

Abstract It is known for decades that dental epithelium and mesenchyme can reconstitute and regenerate a functional tooth. However, the mechanism of tooth reconstitution remains largely unknown due to the lack of an efficient in vitro model. Here, a chemically defined culture system is established that supports tooth reconstitution, further development with normal anatomy, and prompt response to chemical interference in key developmental signaling pathways, termed as toothoids. By using such a system, it is discovered that, during reconstitution, instead of resetting the developmental clock, dental cells reorganized and restarted from the respective developmental stage where they are originally isolated. Moreover, co‐stimulation of Activin A and Hedgehog/Smoothened agonist (SAG) sustained the initial induction of tooth fate from the first branchial arch, which would be otherwise quickly lost in culture. Furthermore, activation of Bone Morphogenetic Protein (BMP) signaling triggered efficient enamel formation in the late‐stage toothoids, without affecting the normal development of ameloblasts. Together, these data highlight the toothoid culture as a powerful tool to dissect the molecular mechanisms of tooth reconstitution and regeneration.
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Research context

OpenAlex topics: dental development and anomalies · Bone and Dental Protein Studies · Dental Trauma and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Center of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 China

Department of Anesthesiology West China Second University Hospital, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education Sichuan University No. 20, Section 3, South Renmin Road Chengdu 610041 China

State Key Laboratory of Oral Disease West China Hospital of Stomatology Sichuan University No. 14, Section 3, South Renmin Road Chengdu 610041 China

Yunnan Key Laboratory of Stomatology Department of Pediatric Dentistry The Affiliated Stomatology Hospital of Kunming Medical University Kunming Medical University No. 1088, Mid‐Haiyuan Road Kunming 650500 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Sichuan University · Major Science and Technology Projects in Yunnan Province · Fundamental Research Funds for the Central Universities

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