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PLoS One. 2018 Jun 25;13(6):e0199632. doi: 10.1371/journal.pone.0199632. eCollection 2018.

Extracellular matrix surface regulates self-assembly of three-dimensional placental trophoblast spheroids.

Author information

Graduate Program in Medical Science, McMaster University, Hamilton, Ontario, Canada.
Department of Pediatrics, McMaster Medical Centre, Hamilton, Ontario, Canada.
Department of Mechanical Engineering, McMaster University, Hamilton, Ontario, Canada.
Evik Diagnostics, Ottawa, Ontario, Canada.


The incorporation of the extracellular matrix (ECM) is essential for generating in vitro models that truly represent the microarchitecture found in human tissues. However, the cell-cell and cell-ECM interactions in vitro remains poorly understood in placental trophoblast biology. We investigated the effects of varying the surface properties (surface thickness and stiffness) of two ECMs, collagen I and Matrigel, on placental trophoblast cell morphology, viability, proliferation, and expression of markers involved in differentiation/syncytial fusion. Most notably, thicker Matrigel surfaces were found to induce the self-assembly of trophoblast cells into 3D spheroids that exhibited thickness-dependent changes in viability, proliferation, syncytial fusion, and gene expression profiles compared to two-dimensional cultures. Changes in F-actin organization, cell spread morphologies, and integrin and matrix metalloproteinase gene expression profiles, further reveal that the response to surface thickness may be mediated in part through cellular stiffness-sensing mechanisms. Our derivation of self-assembling trophoblast spheroid cultures through regulation of ECM surface alone contributes to a deeper understanding of cell-ECM interactions, and may be important for the advancement of in vitro platforms for research or diagnostics.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Dr. Tom Ewart, a member of our research team, is employed by Evik Diagnostics, Ottawa Canada. Dr. Ewart provides in-kind consultancy for this expertise in surface chemistry and its connection to 3 dimensional cell culture growth. His involvement in this project is purely academic and this commercial affiliation does not alter our adherence to all PLOS ONE policies on sharing data and materials.

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