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Data for organotypic stem cell model for human embryonic palatal fusion.

Metadata Updated: November 12, 2020

Cleft palate (CP) is a common birth defect, occurring in an estimated 1 in 1000 births worldwide. The secondary palate is formed by paired palatal shelves that grow toward each other, appose, attach and fuse. CP can result from disruption of any of these processes. The palatal shelves basically consist of a mesenchymal tissue core covered with a layer of epithelial cells. One of the mechanisms that can cause CP is failure of fusion, i.e., failure to remove the epithelial seam between the palatal shelves to allow the mesenchyme to merge and form a continuous palate. This process requires complex interactions between mesenchymal and epithelial cells, and signaling components such as growth factors. Epidermal growth factor (EGF) plays an important role in palate growth and differentiation, while it may impede fusion. We developed a 3D organotypic model using human mesenchymal and epithelial stem cells to mimic human embryonic palatal shelves, and tested its functional relevance by monitoring 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 by culture medium and evaluated for osteogenic differentiation. Heterotypic spheroids, or organoids, were constructed by coating hMSC spheroids with MaxGel™ extracellular matrix solution followed by a layer of human progenitor epithelial keratinocytes (hPEK). Organoids were incubated in co-culture medium with or without hEGF and assessed for cell proliferation and spheroid pairs were assessed for time to fusion. Osteogenic differentiation in hMSC spheroids was highest by day 13. hEGF delayed fusion of heterotypic organoids after 12 and 18 hours of contact. hEGF increased proliferation in organoids at 4 ng/ml, and proliferation was detected in hPEKs alone on microcarrier beads, suggesting a potential mechanism for delayed fusion by hEGF. Our results show that this model of human palatal fusion consisting of a core of differentiated hMSCs with a hPEK outer layer appropriately mimics the morphology of the developing human palate and responds to hEGF as expected. Future studies will focus on using the organoid model to evaluate the effects of teratogenic chemicals on palatal fusion, and validating the results.

This dataset is associated with the following publication: Wolf, C., D. Belair, C. Becker, K. Das, J. Schmid, and B. Abbott. Development of an organotypic stem cell model for the study of human embryonic palatal fusion. BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, USA, 1322-1334, (2018).

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Public: This dataset is intended for public access and use. License: See this page for license information.

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Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020
Publisher U.S. EPA Office of Research and Development (ORD)
Data Last Modified 2018-04-13
Public Access Level public
Bureau Code 020:00
Schema Version
Harvest Object Id 37c98e7b-425e-43d1-ab4f-e64e73ae1cda
Harvest Source Id 04b59eaf-ae53-4066-93db-80f2ed0df446
Harvest Source Title EPA ScienceHub
Program Code 020:000
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents
Source Datajson Identifier True
Source Hash 51c0a2e96eaf8199ee796c723a147ad2e8877a10
Source Schema Version 1.1

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