Cell culture dimensionality influences mesenchymal stem cell fate through cadherin-2 and cadherin-11

Fiona R. Passanha, Thomas Geuens, Simon Konig, Clemens A. van Blitterswijk, Vanessa L. S. LaPointe*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

Abstract

The acquisition of a specific cell fate is one of the core aims of tissue engineering and regenerative medicine. Significant evidence shows that aggregate cultures have a positive influence on cell fate decisions, presumably through cell-cell interactions, but little is known about the specific mechanisms. To investigate the difference between cells cultured as a monolayer and as aggregates, we started by looking at cadherin expression, an important protein involved in cell adhesion, during the differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in aggregate and monolayer cultures. We observed that proliferating hMSCs in monolayer culture expressed lower levels of cadherin-2 and increased cadherin-11 expression at cell-cell contact sites over time, which was not evident in the aggregate cultures. By knocking down cadherin-2 and cadherin-11, we found that both cadherins were required for adipogenic differentiation in a monolayer as well as aggregate culture. However, during osteogenic differentiation, low levels of cadherin-2 were found to be favorable for cells cultured as a monolayer and as aggregates, whereas cadherin- 11 was dispensable for cells cultured as aggregates. Together, these results provide compelling evidence for the important role that cadherins play in regulating the differentiation of hMSCs and how this is affected by the dimensionality of cell culture.

Original languageEnglish
Article number120127
Number of pages10
JournalBiomaterials
Volume254
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Cell-cell contact
  • Osteogenic differentiation
  • Adipogenic differentiation
  • hMSCs
  • Aggregate culture
  • Monolayer culture
  • N-CADHERIN
  • STROMAL CELLS
  • DIFFERENTIATION
  • 3D
  • EXPRESSION
  • ADHESION
  • 2D
  • AGGREGATION
  • ACTIVATION
  • DIVERSITY

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