Consistent apparent Young's modulus of human embryonic stem cells and derived cell types stabilized by substrate stiffness regulation promotes lineage specificity maintenance

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Apparent Young's modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established. Results Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types. Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics. On substrates that wer

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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