ArticleStem cell research & therapy2019
Sequential stimulation with different concentrations of BMP4 promotes the differentiation of human embryonic stem cells into dental epithelium with potential for tooth formation.
Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Tooth-on-a-chip to engineer early dental epithelial-mesenchymal interaction.Materials today. Bio · 2025Article
- Next-Generation Strategies for Enamel Repair and Regeneration: Advances in Biomaterials and Translational Challenges.Tissue engineering and regenerative medicine · 2025Review
- The comprehensive progress of tooth regeneration from the tooth development to tissue engineering and clinical application.Cell regeneration (London, England) · 2025Review
- Low-Intensity Pulsed Ultrasound Promotes Osteogenesis in Porous Titanium Alloys Through miR-1187/BMP4 Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells.Biomedicines · 2024Review
- Tissue Regeneration on Rise: Dental Hard Tissue Regeneration and Challenges-A Narrative Review.Scientifica · 2024Review
- A sono-responsive antibacterial nanosystem co-loaded with metformin and bone morphogenetic protein-2 for mitigation of inflammation and bone loss in experimental peri-implantitis.Frontiers in bioengineering and biotechnology · 2024Article
- Role and Mechanism of BMP4 in Regenerative Medicine and Tissue Engineering.Annals of biomedical engineering · 2023Review
- Fabrication of functional ameloblasts from hiPSCs for dental application.Frontiers in cell and developmental biology · 2023Article
- Transcriptomic Network Regulation of Rat Tooth Germ from Bell Differentiation Stage to Secretory Stage: MAPK Signaling Pathway Is Crucial to Extracellular Matrix Remodeling.BioMed research international · 2023Article
- Strategies for Mammalian Mesenchymal Stem Cells Differentiation into Primordial Germ Cell-Like Cells: A Review.Cell journal · 2022Article
- FGF10 ameliorates lipopolysaccharide-induced acute lung injury in miceFrontiers in pharmacology · 2022Article
- BMP4-regulated human dental pulp stromal cells promote pulp-like tissue regeneration in a decellularized dental pulp matrix scaffold.Odontology · 2021Article
- Identification of bone morphogenetic protein 4 in the saliva after the placement of fixed orthodontic appliance.Progress in orthodontics · 2021Observational
- Regulation of bone morphogenetic protein 4 on epithelial tissue.Journal of cell communication and signaling · 2020Review
- Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update.Stem cells international · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTooth loss caused by caries or injuries has a negative effect on human health; thus, it is important to develop a reliable method of tooth regeneration. Research on tooth regeneration has mainly focused on mouse pluripotent stem cells, mouse embryonic stem cells, and adult stem cells from various sources in mice, whereas little has examined the differentiation of human embryonic stem (hES) cells into dental epithelium (DE) and odontogenic potential in vivo.
methodsIn this study, we induced hES cells to differentiate into dental epithelium using different concentrations of bone morphogenetic protein 4 (BMP4). With 1 pM BMP4, the hES cells differentiated into oral ectoderm (OE). These cells were then stimulated with 30 pM BMP4. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence showed the differentiation of OE and DE. The DE generated was mixed with embryonic day 14.5 mouse dental mesenchyme (DM) and transplanted into the renal capsules of nude mice. Thirty days later, the resulting tooth-like structures were examined by micro-computed tomography and hematoxylin and eosin staining.
resultsAfter 4 days of 1 pM BMP4 stimulation, Pitx1-positive OE formed. qRT-PCR and immunofluorescence revealed that induction with 30 pM BMP4 for 2 days caused the OE to differentiate into Pitx2/Dlx2/AMBN-positive DE-like cells. These cells also expressed β-catenin and p-Smad1/5/8, which are key proteins in the Wnt/β-catenin and Bmp signaling pathways, respectively. Thirty days after in vivo transplantation, six teeth with enamel and dentin had formed on the kidney.
conclusionsThese results show that hES cells differentiated into DE after sequential stimulation with different concentrations of BMP4, and the DE thus generated showed odontogenic potential.
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