Disease-specific extracellular matrix composition regulates placental trophoblast fusion efficiency

Prabu Karthick Parameshwar, Lucas Sagrillo-Fagundes, Caroline Fournier, Sylvie Girard, Cathy Vaillancourt, Christopher Moraes

Research output: Contribution to journalArticlepeer-review

Abstract

The placental syncytiotrophoblast is a multinucleated layer that regulates transport between the mother and fetus. Fusion of trophoblasts is essential to form this layer, but this process can be disrupted in pregnancy-related disorders such as preeclampsia. Disease progression is also associated with changes in the extracellular matrix (ECM), but whether disease-specific ECM compositions play any causal role in establishing syncytiotrophoblast disease phenotypes remains unknown. Here, we develop a decellularization-based platform to isolate and characterize the role of human placental ECM composition on cell function, while controlling for the confounding effects of matrix structure and mechanics that can arise in conventional tissue decellularization/recellularization experiments. Using this approach, we demonstrate that ECM compositional changes that occur in preeclampsia have a statistically significant effect on adhesion, spreading, and fusion of placental trophoblasts. Proteomic analysis of ECM content then allowed us to identify and recreate selected differences in matrix composition; indicating that replacement of normally present Type IV Collagen by Type I Collagen in preeclampsia significantly affects fusion efficiency. These results indicate that disease-specific matrix compositions can play an important role in trophoblast fusion, suggesting novel matrix-targeting therapeutic strategies for pregnancy-related disorders. More broadly, this work demonstrates the utility of a decellularization-based approach in understanding the functional contributions of matrix composition in driving cellular disease phenotypes. This journal is

Original languageEnglish (US)
Pages (from-to)7247-7256
Number of pages10
JournalBiomaterials Science
Volume9
Issue number21
DOIs
StatePublished - Nov 7 2021

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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