ArticleBirth defects research2018
Development of an organotypic stem cell model for the study of human embryonic palatal fusion.
Article in Birth defects research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- An improved multicellular human organoid model for the study of chemical effects on palatal fusion.Birth defects research · 2023Article
- Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review.Annals of medicine · 2022Review
- Allele-specific transcription factor binding in a cellular model of orofacial clefting.Scientific reports · 2022Article
- Cell spheroid fusion: beyond liquid drops model.Scientific reports · 2020Article
- Gene-environment interactions: aligning birth defects research with complex etiology.Development (Cambridge, England) · 2020Review
- Characterizing cleft palate toxicants using ToxCast data, chemical structure, and the biomedical literature.Birth defects research · 2020Article
- Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction.Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCleft palate (CP) is a common birth defect, occurring in an estimated 1 in 1,000 births worldwide. The secondary palate is formed by paired palatal shelves, consisting of a mesenchymal core with an outer layer of epithelial cells that grow toward each other, attach, and fuse. One of the mechanisms that can cause CP is failure of fusion, that is, failure to remove the epithelial seam between the palatal shelves to allow the mesenchyme confluence. Epidermal growth factor (EGF) plays an important role in palate growth and differentiation, while it may impede fusion.
methodsWe developed a 3D organotypic model using human mesenchymal and epithelial stem cells to mimic human embryonic palatal shelves, and tested the effects of human EGF (hEGF) on proliferation and fusion. Spheroids were generated from human umbilical-derived mesenchymal stem cells (hMSCs) directed down an osteogenic lineage. Heterotypic spheroids, or organoids, were constructed by coating hMSC spheroids with extracellular matrix solution followed by a layer of human progenitor epithelial keratinocytes (hPEKs). Organoids were incubated in co-culture medium with or without hEGF and assessed for cell proliferation and time to fusion.
resultsOsteogenic differentiation in hMSC spheroids was highest by Day 13. hEGF delayed fusion of organoids after 12 and 18 hr of contact. hEGF increased proliferation in organoids at 4 ng/ml, and proliferation was detected in hPEKs alone.
conclusionOur results show that this model of human palatal fusion appropriately mimics the morphology of the developing human palate and responds to hEGF as expected.
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Registered trials
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