| Popis: |
Brain organoids are self-assembled, three-dimensionally structured tissues that are typically derived from pluripotent stem cells. They are multicellular aggregates that can more accurately recapitulate the tissue microenvironment compared to other cell culture systems and also reproduce organ function. These stem cell-derived 3D tissues can be excellent models for investigating mechanisms of tissue formation and responses to physiological and mechanical cues. However, understanding about their mechanical properties pales in comparison, which is all the more galling in light of newfound insights about how mechanical stimuli trigger the onset of neurodegenerative conditions. Herein, formative steps are taken to fill this knowledge gap, using neurospheres were generated from murine neural stem cells and subjected to compressive forces. I generated neurospheres that exhibit stress relaxation under static compression and viscoelastic behavior at low strains. The suitability of the Tatara model for characterizing the mechanical properties of neurospheres was also evaluated. Besides, the utility of cantilevered capillary force apparatus as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres was demonstrated. Neurospheres exhibit viscoelasticity consistent with neural tissue and document a size-dependence of their elastic moduli. Oxidative stress altered the composition, architecture and signaling within the tissues. I observed a clear correlation between oxidative stress, the chemical state of the tissues and their biophysical properties. My results confirms that non-cytotoxic oxidative stress can modulate the differentiation of neural progenitor cells. This is the first study of its kind to investigate the mechanical properties of in vitro 3D tissues. Moreover, the methodologies developed can also be used to improve the quality and safety of cell and tissue biomanufacturing processes and yields insights for establishing rheological measurements as biomarkers. |
