Laboratoire Matière et Systèmes Complexes

Organoids : a bottom-up approach to development

Sara Bonavia - MSC

Embryonic development proceeds through an ordered succession of cell fate determination and collective migration steps. The mechanisms underlying such a conserved and reproducible process are not fully unveiled yet. In mammalians, the study of development is furthermore limited by the embryo not being available to observations, and, when it comes to humans, ethics.

During recent years Embryonic Stem Cells (ESC) have proven to be a promising tool to investigate development in vitro. The availability of synthetic systems allows for observations and manipulations that were previously impossible. The ability of Embryonic Stem Cells to differentiate to all progenitors of the adult body makes them a good candidate to investigate cell fate determination. Moreover, numerous recent studies have shown that particular cell culture conditions can trigger ESCs’ self-organisation that recapitulate the early morphogenetic rearrangements taking place in vivo.

I will present which culture conditions enable us to grow mouse Embryonic Organoids that recapitulate the apico-basal polarization and luminogenesis, that the embryo undergoes during the peri-implantation stage. At this stage, gastrulation would lead to the rearrangement of the embryo into three layers of progenitor cells (germ layers) and the establishment of the antero-posterior axis. This process is known to be regulated by the BMP and TGF-ß signalling pathways. I will show how our synthetic system responds to these gastrulation-inducing stimuli, when provided uniformly along with culture media and how we make use of microfluidics to tailor a chemically defined culture environment, where morphogens are provided in a gradient, with the aim of inducing symmetry breaking and increasing the reproducibility among the organoid population.

Gold nanoparticles biotransformation in intracellular medium

Alice Balfourier - MSC

While gold nanoparticles (GNPs) are used in an expanding spectrum of biomedical applications, questioning remains about their transformations in biological medium. These biotransformations can affect their therapeutic properties as well as their toxicity or life cycle, and therefore be an obstacle to their large scale use. We focus our study on two types of biotransformations, aggregation and biodegradation of GNPs in lysosome medium. GNPs aggregation modify their optical properties, and thus their therapeutic potential. We use an approach that combine a relation-structure study of GNPs aggregates in model medium, and in vitro experiment to elucidate the impact of uncontrolled aggregation on therapeutic effects. We reveal that simple citrate-coated spherical GNPs could be interesting inside cells despite their poor properties before internalisation. Then, I will present our results on GNPs degradation inside cells, a process that generate puzzling self-assembled gold structures (see figure below). After a description of this two-step process, i.e. dissolution and recrystallization of GNPs, we will compare biodegraded GNPs to previously observed recrystallization structures obtained with therapeutic gold salts. This comparison evidences a gold metabolism common to crystallized and ionic gold, and offer new perspectives for GNPs use for therapy.