Abstract

Embryoid bodies (EBs) resemble self-organizing aggregates of pluripotent stem cells that recapitulate some aspects of early embryogenesis. Within few days, the cells undergo a transition from rather homogeneous epithelial-like pluripotent stem cell colonies into a three-dimensional organization of various cell types with multifaceted cell–cell interactions and lumen formation—a process associated with repetitive epithelial-mesenchymal transitions. In the last few years, culture methods have further evolved to better control EB size, growth, cellular composition, and organization—e.g., by the addition of morphogens or different extracellular matrix molecules. There is a growing perception that the mechanical properties, cell mechanics, and cell signaling during EB development are also influenced by physical cues to better guide lineage specification; substrate elasticity and topography are relevant, as well as shear stress and mechanical strain. Epithelial structures outside and inside EBs support the integrity of the cell aggregates and counteract mechanical stress. Furthermore, hydrogels can be used to better control the organization and lineage-specific differentiation of EBs. In this review, we summarize how EB formation is accompanied by a variety of biomechanical parameters that need to be considered for the directed and reproducible self-organization of early cell fate decisions.

Highlights

  • The first report of embryoid bodies (EBs) dates back to the mid-seventies, before the advent of embryonic stem cell (ESC) research [1]

  • These results suggest that ESCs cultured in 3D microwells exhibit a more epithelial phenotype, possibly due to the increased cell–cell contact to neighboring cells [12]

  • After stimulation in a 0.2 Tesla magnetic field for one hour, cells within the Embryoid bodies (EBs) started to activate Protein Kinase A (PKA) expression and increased levels of phosphorylated extracellular signal-regulated kinase 1/2, both of which are associated with integrin activation

Read more

Summary

Introduction

The first report of embryoid bodies (EBs) dates back to the mid-seventies, before the advent of embryonic stem cell (ESC) research [1]. The ability to form 3D structures that mimic early embryogenesis is inherent to all pluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells [2] The latter can be reprogrammed from virtually any cell of the body and shares many important characteristics with ESCs [3,4]. In comparison to conventional 2D culture, the differentiation of 3D aggregates of pluripotent stem cells leads to increased induction into mesoderm and endoderm and the differential expression of genes that regulate developmental processes [12]. It is important to choose the best suited starting material and culture conditions to determine the effects of different mechanical stimuli on the cell fate decisions of aggregated pluripotent stem cells. We discuss the relevance of cell mechanics during EB differentiation and how mechanical stimulation affects the behavior and function of pluripotent stem cells in 3D aggregates

Methods of Embryoid Body Formation
Molecular Changes during Embryoid Body Formation
Cell Mechanics and Lineage Specification in Embryoid Bodies
Molecular Pathways that Trigger the Cell-Mechanic Changes during EBs
The Size of Stem Cell Aggregates Modulates Their Differentiation Potential
Effect of Shear Stress on Embryoid Body Differentiation
Impact of Mechanical Strain on EBs
Hydrogels for EB Differentiation
Findings
Conclusions
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.