Biology subjects

Di Cio, S.

Publications and source records attributed to Di Cio, S..

3 recordsLinked to original sources

bioRxiv2025

Artificial Cells Evidence Apical Compressive Forces Building up During Neuroepithelial Organoid Early Development

During early stages of development of cerebral organoids, budding neuroepithelia display striking changes in size and morphology, occurring very rapidly. Whilst mechanical forces mediated by cadherin-cadherin junctions are known to control the assembly, maturation and stability of epithelia, little is known of the mechanical context associated with neuroepithelial organoid development. In this report, we demonstrate a rapid translocation of YAP to budding neuroepithelial apical junctions, suggesting the build-up of strong compressive forces early on in their development. To study the mechanics of budding rosettes, we designed oil microdroplets stabilised by protein nanosheets displaying cadherin receptors, able to engage with receptors presented by neighbouring neuroepithelial cells, to integrate into embryoid bodies and developing organoids. The resulting artificial cells are able to sustain the formation of mature junctions with neighbouring cells and lead to the recruitment of tight junction maturation proteins such as ZO1. During early budding of neuroepithelial rosettes, artificial cells are found to be rapidly expelled from the developing organoids, further evidencing apical compressive forces. These forces are not opposed by sufficiently strong shear forces from neighbouring cells, or adhesive forces maintaining anchorage to the apical junction, to induce deformation of artificial cells.

bioengineering↗

bioRxiv2024

Hybrid cancer stem cells utilise vascular tracks for collective streaming invasion in a metastasis-on-a-chip device

Cancer stem cells (CSCs) drive cancer metastatic dissemination. They do not do so in a vacuum, and the important influence of the tumour microenvironment (TME) on metastatic dissemination is becoming increasingly recognised. Therapeutic targeting of CSC-TME interactions may be a promising route to suppression of tumour metastasis. However, we must first understand how interactions with the TME influence CSC metastatic dissemination. To achieve this understanding, there is a need for experimental models that enable the analysis of dynamic interactions at single cell resolution within a complex environment. To this end, we utilise a metastasis-on-a-chip device to produce a 3D in vitro model of CSC interaction with a developing microvasculature, that is amenable to precise imaging and real time studies at single cell resolution. We show that the invasive phenotype of oral squamous cell carcinoma (OSCC) cells is markedly altered when in proximity to a microvasculature, with a switch to a hybrid CSC phenotype that undergoes collective streaming invasion. Mechanistically, ECM compression by the developing vasculature creates an environment that is refractory to cancer invasion, whilst leaving abandoned vascular tracks that can be utilised by hybrid CSCs for collective streaming invasion. Human tissue studies identify streaming invasion in association with vascularised regions in OSCC specimens. These findings elucidate the influence of the vasculature on CSC metastatic dissemination in OSCC, and the role of hybrid CSC invasion plasticity in overcoming this TME constraint.

cancer biology↗

bioRxiv2022

Impact of Pericytes on the Stabilisation of Microvascular Networks in Microfluidic Systems in Response to Nanotoxicity

Recapitulating the normal physiology of the microvasculature is pivotal in the development of more complex in vitro models and organ-on-chip design. Pericytes are an important component of the vasculature, promoting vessel stability, inhibiting vascular permeability and maintaining the vascular hierarchical architecture. This report presents a microfluidic model exploring interactions between endothelial cells and pericytes. We identify basal conditions required to form stable and reproducible endothelial networks. We then investigate interactions between endothelial cells and pericytes via direct co-culture. In our system, pericytes inhibited vessel hyperplasia and maintained vessel length in prolonged culture (>10 days). In addition, these vessels displayed barrier function and expression of junction markers associated with vessel maturation, including VE-cadherin, {beta}-catenin and ZO-1. Furthermore, pericytes maintained vessel integrity following stress (nutrient starvation) and inhibited vessel regression, in contrast to the striking dissociation of networks in endothelial monocultures. This response was also observed when endothelial/pericyte co-cultures were exposed to high concentrations of moderately toxic cationic nanoparticles used for gene delivery. This study highlights the importance of pericytes in protecting vascular networks from stress and external agents and their importance to the design of advanced in vitro models, including for the testing of nanotoxicity, to better recapitulate physiological response and avoid false positives.

bioengineering↗