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

• Published in: Journal of advanced research Vol. 61; pp. 119 - 131
• Main Authors: Kim, Eun-Jung, Kim, Ka-Hwa, Kim, Hyun-Yi, Lee, Dong-Joon, Li, Shujin, Ngoc Han, Mai, Jung, Han-Sung
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01.07.2024; Elsevier
• Subjects: Cell Differentiation; Cells, Cultured; Epithelial Cells - cytology; Epithelial Cells - metabolism; Extracellular Matrix - metabolism; Humans; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Neural Crest - cytology; Osteogenesis; Tissue Engineering - methods; Tooth - cytology
• ISSN: 2090-1232; 2090-1224; 2090-1224
• DOI: 10.1016/j.jare.2023.08.012

[Display omitted] •hiPSCs are differentiated into dental epithelial and mesenchymal cells, identified by RNA sequencing analysis.•hiPSC-derived dental cells encapsulated in GelMA led to the capacity for osteogenic and chondrogenic lineages.•Differentiated dental cells in collagen gel induced into chondrogenic or osteogenic lineage.•Our most significant finding is the successful formation of bioengineered tooth-like constructs from hiPSC-derived dental cells in agar gel, a breakthrough in the field of bioengineering. 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. 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. 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. 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. 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.