1,721,045 research outputs found
From Pluripotent Stem Cells to Organoids and Bioprinting: Recent Advances in Dental Epithelium and Ameloblast Models to Study Tooth Biology and Regeneration
No full textAmeloblasts are the specialized dental epithelial cell type responsible for enamel formation. Following completion of enamel development in humans, ameloblasts are lost and biological repair or regeneration of enamel is not possible. In the past, in vitro models to study dental epithelium and ameloblast biology were limited to freshly isolated primary cells or immortalized cell lines, both with limited translational potential. In recent years, large strides have been made with the development of induced pluripotent stem cell and organoid models of this essential dental lineage – both enabling modeling of human dental epithelium. Upon induction with several different signaling factors (such as transforming growth factor and bone morphogenetic proteins) these models display elevated expression of ameloblast markers and enamel matrix proteins. The advent of 3D bioprinting, and its potential combination with these advanced cellular tools, is poised to revolutionize the field – and its potential for tissue engineering, regenerative and personalized medicine. As the advancements in these technologies are rapidly evolving, we evaluate the current state-of-the-art regarding in vitro cell culture models of dental epithelium and ameloblast lineage with a particular focus toward their applicability for translational tissue engineering and regenerative/personalized medicine.This work was supported by grants from KU Leuven (Research Fund) and Fund for Scientific Research (FWO) Flanders. FH was supported by a FWO project grant (G061819FWO) and SH by a BOF UHasselt funding (BOF22KP12).
Acknowledgements
We are grateful to all members of the Laboratory for Research in Ischemic Stroke, Stem Cells and Angiogenesis (LISSA, Hasselt University) and the Laboratory for Tissue Plasticity in Health and Disease (KU Leuven). Figures were created using Adobe Illustrator and BioRender.com
Establishing Organoids from Human Tooth as a Powerful Tool toward Mechanistic Research and Regenerative Therapy
No full textTeeth are of key importance in life not only for food mastication and speech but also for psychological well-being. Knowledge on human tooth development and biology is scarce. In particular, not much is known about the tooth's epithelial stem cells and their function. We succeeded in developing a novel organoid model starting from human tooth tissue (i.e., dental follicle, isolated from extracted wisdom teeth). The organoids are robustly and long-term expandable and recapitulate the proposed human tooth epithelial stem cell compartment in terms of marker expression as well as functional activity. In particular, the organoids are capable to unfold an ameloblast differentiation process as occurring in vivo during amelogenesis. This unique organoid model will provide a powerful tool to study not only human tooth development but also dental pathology, and may pave the way toward tooth-regenerative therapy. Replacing lost teeth with a biological tooth based on this new organoid model could be an appealing alternative to the current standard implantation of synthetic materials.sponsorship: We are grateful to all staff members of the Oral and Maxillofacial Surgery (MKA) of UZ Leuven, as well as the patients, for their invaluable help in collecting freshly extracted third molars. We would also like to thank Dr. Reinhilde Jacobs and Dr. Elisabeth Tijskens for their help with the sample collection. This work was supported by grants from KU Leuven (BOF) and FWO-Flanders (G061819N). L.H. is an FWO Ph.D. Fellow (1S84718N). (KU Leuven (BOF), FWO-Flanders|G061819N, FWO|1S84718N)status: Publishe
Intertwined Signaling Pathways Governing Tooth Development: A Give-and-Take Between Canonical Wnt and Shh
No full textTeeth play essential roles in life. Their development relies on reciprocal interactions between the ectoderm-derived dental epithelium and the underlying neural crest-originated mesenchyme. This odontogenic process serves as a prototype model for the development of ectodermal appendages. In the mouse, developing teeth go through distinct morphological phases that are tightly controlled by epithelial signaling centers. Crucial molecular regulators of odontogenesis include the evolutionarily conserved Wnt, BMP, FGF and sonic hedgehog (Shh) pathways. These signaling modules do not act on their own, but are closely intertwined during tooth development, thereby outlining the path to be taken by specific cell populations including the resident dental stem cells. Recently, pivotal Wnt-Shh interaction and feedback loops have been uncovered during odontogenesis, showing conservation in other developing ectodermal appendages. This review provides an integrated overview of the interplay between canonical Wnt and Shh throughout mouse tooth formation stages, extending from the initiation of dental placode to the fully formed adult tooth.sponsorship: This work was supported by a grant of the Fund for Scientific Research-Flanders (FWO) (G061819N). LH is an FWO Ph.D. fellow (1S84718N). (Fund for Scientific Research-Flanders (FWO)|G061819N, FWO|1S84718N)status: Publishe
Establishment of inclusive single-cell transcriptome atlases from mouse and human tooth as powerful resource for dental research
No full textSingle-cell (sc) omics has become a powerful tool to unravel a tissue's cell landscape across health and disease. In recent years, sc transcriptomic interrogation has been applied to a variety of tooth tissues of both human and mouse, which has considerably advanced our fundamental understanding of tooth biology. Now, an overarching and integrated bird's-view of the human and mouse tooth sc transcriptomic landscape would be a powerful multi-faceted tool for dental research, enabling further decipherment of tooth biology and development through constantly progressing state-of-the-art bioinformatic methods as well as the exploration of novel hypothesis-driven research. To this aim, we re-assessed and integrated recently published scRNA-sequencing datasets of different dental tissue types (healthy and diseased) from human and mouse to establish inclusive tooth sc atlases, and applied the consolidated data map to explore its power. For mouse tooth, we identified novel candidate transcriptional regulators of the ameloblast lineage. Regarding human tooth, we provide support for a developmental connection, not advanced before, between specific epithelial compartments. Taken together, we established inclusive mouse and human tooth sc atlases as powerful tools to potentiate innovative research into tooth biology, development and disease. The maps are provided online in an accessible format for interactive exploration.sponsorship: This work was supported by grants from the KU Leuven Research Fund and from the FWO (G061819N). LH is an FWO PhD fellow (1S84718N). (KU Leuven Research Fund, FWO|G061819N, FWO PhD fellow, 1S84718N)status: Publishe
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