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Engineering Epithelial-Mesenchymal Microtissues to Study Cell-Cell Interactions in Development.

Jacob I Reynolds1, Ross A Vitek2, Peter G Geiger2

  • 1Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.

Methods in Molecular Biology (Clifton, N.J.)
|December 16, 2021
PubMed
Summary
This summary is machine-generated.

Researchers developed a microphysiological system to model human development, enabling the study of orofacial clefts. This scalable system recreates epithelial-mesenchymal interactions crucial for embryonic growth.

Keywords:
3D extracellular matrixCleft lipEpithelial mesenchymal cross-talkPalateParacrine signalingSignaling gradient

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Area of Science:

  • Developmental Biology
  • Tissue Engineering
  • Biomaterials Science

Background:

  • Human development relies on intercellular signaling, but in vitro models lack tissue architecture and scalability.
  • Orofacial development, including lip and palate formation, depends on paracrine signaling via pathways like Sonic Hedgehog (SHH).

Purpose of the Study:

  • To develop a scalable microphysiological system for modeling epithelial-mesenchymal interactions in orofacial development.
  • To create a robust in vitro model for studying normal and abnormal embryonic facial growth.

Main Methods:

  • Engineered microplates were created using CNC micromilling of 96-well plates to house epithelial-mesenchymal microtissues.
  • A 3D mesenchyme was formed by embedding cells in hydrogel, followed by overlaying an epithelial layer in microchannels.
  • The system facilitates high-content imaging due to an epithelial-mesenchymal interface on and perpendicular to the imaging plane.

Main Results:

  • The microphysiological system successfully models epithelial-mesenchymal interactions relevant to orofacial development.
  • The microtissues are compatible with various analytical techniques, including reporter assays and gene expression analysis.
  • The engineered microplate system is scalable and throughput-compatible.

Conclusions:

  • This tractable microphysiological system provides a novel approach to study intercellular signaling in embryonic development.
  • The model holds promise for advancing our understanding of orofacial development and related congenital anomalies.