Harnessing the dental cells derived from human induced pluripotent stem cells for hard tissue engineering

Eun-Jung Kim; Ka-Hwa Kim; Hyun-Yi Kim; Dong-Joon Lee; Shujin Li; Mai Ngoc Han; Han-Sung Jung

doi:10.1016/j.jare.2023.08.012

Harnessing the dental cells derived from human induced pluripotent stem cells for hard tissue engineering

J Adv Res. 2023 Aug 22:S2090-1232(23)00228-X. doi: 10.1016/j.jare.2023.08.012. Online ahead of print.

Authors

Eun-Jung Kim¹, Ka-Hwa Kim², Hyun-Yi Kim³, Dong-Joon Lee⁴, Shujin Li⁵, Mai Ngoc Han⁶, Han-Sung Jung⁷

Affiliations

¹ Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea. Electronic address: blueleah@yuhs.ac.
² Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea. Electronic address: kahwa@yuhs.ac.
³ NGeneS Inc., Ansan-si 15495, Korea. Electronic address: hykim@ngenes.co.kr.
⁴ Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea. Electronic address: dongjoon@yuhs.ac.
⁵ Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea. Electronic address: lsj10026@yuhs.ac.
⁶ Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea. Electronic address: maingochan244@gmail.com.
⁷ Division in Anatomy and Developmental Biology, Department of Oral Biology, Taste Research Center, Oral Science Research Center, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul 03722, Korea. Electronic address: hsjung@yuhs.ac.

PMID: 37619933
DOI: 10.1016/j.jare.2023.08.012

Abstract

Introduction: Most mineralized tissues in our body are present in bones and teeth. Human induced pluripotent stem cells (hiPSCs) are promising candidates for cell therapy to help regenerate bone defects and teeth loss. The extracellular matrix (ECM) is a non-cellular structure secreted by cells. Studies on the dynamic microenvironment of ECM are necessary for stem cell-based therapies.

Objectives: We aim to optimize an effective protocol for hiPSC differentiation into dental cells without utilizing animal-derived factors or cell feeders that can be applied to humans and to mineralize differentiated dental cells into hard tissues.

Methods: For the differentiation of both dental epithelial cells (DECs) and dental mesenchymal cells (DMCs) from hiPSCs, an embryoid body (EB) was formed from hiPSCs. hiPSC were differentiated into neural crest cells with an induction medium utilized in our previous study, and hiPSC-derived DECs were differentiated with a BMP-modulated customized medium. hiPSC-dental cells were then characterized, analyzed, and validated with transcriptomic analysis, western blotting, and RT-qPCR. To form mineralized tissues, hiPSC-derived DECs were recombined with hiPSC-derived DMCs encapsulated in various biomaterials, including gelatin methacryloyl (GelMA), collagen, and agar matrix.

Results: These hiPSC-derived dental cells are highly osteogenic and chondro-osteogenic in photocrosslinkable GelMA hydrogel and collagen type I microenvironments. Furthermore, hiPSC-derived dental cells in agar gel matrix induced the formation of a bioengineered tooth.

Conclusion: Our study provides an approach for applying hiPSCs for hard tissue regeneration, including tooth and bone. This study has immense potential to provide a novel technology for bioengineering organs for various regenerative therapies.