Tissue-engineered multi-cellular models of the uterine wall

Tatyana Kuperman, Mark Gavriel, Ruth Gotlib, Ying Zhang, Ariel Jaffa, David Elad*, Dan Grisaru

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The human uterus is composed of three layers: endometrium, myometrium and perimetrium. It remodels during the monthly menstrual cycle and more significantly during the complex stages of reproduction. In vivo studies of the human uterine wall are yet incomplete due to ethical and technical limitations. The objective of this study was to develop in vitro uterine wall models that mimic the in vivo structure in humans. We co-cultured multiple cellular models of endometrial epithelial cells, endometrial stromal cells and smooth muscle cells on a synthetic membrane mounted in multi-purpose custom-designed wells. Immunofluorescence staining and confocal imaging confirmed that the new model represents the in vivo anatomical architecture of the inner uterine wall. Hormonal treatment with progesterone and β-estradiol demonstrated increased expression of progestogen-associated endometrial protein, which is associated with the in vivo receptive uterus. The new tissue-engineered in vitro models of the uterine wall will enable deeper investigation of molecular and biomechanical aspects of the blastocyst–uterus interaction during the window of implantation.

Original languageEnglish
Pages (from-to)1629-1639
Number of pages11
JournalBiomechanics and Modeling in Mechanobiology
Volume19
Issue number5
DOIs
StatePublished - 1 Oct 2020

Keywords

  • Custom-designed well
  • In vitro model
  • Multi-cellular co-culture
  • Progesterone
  • Receptive uterus
  • β-Estradiol

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