Des interactions intégrine-collagène IV au développement d'une plateforme microfluidique intégrant des capteurs en vue d'une barrière de filtration glomérulaire sur puce

Chronic kidney disease affects more than 10% of the global population and represents a major public health challenge with limited therapeutic options. Current treatments, such as dialysis and kidney transplantation, are associated with reduced life expectancy, high economic costs, and significant inequalities in access to care. To better understand the mechanisms underlying these diseases and to develop new therapeutic strategies, reliable experimental models of kidney function are essential. Traditional approaches, based on animal experimentation or 2D cell culture, have enabled major advances but fail to reproduce the structural and functional complexity of the glomerular filtration barrier (GFB).In recent years, microphysiological systems, and in particular organ-on-chip (OoC) technologies, have emerged as promising alternatives capable of reproducing organ-level functions in controlled microenvironments. Although several glomerulus-on-chip devices have been developed internationally, they still present important limitations, such as non-physiological basement membranes, a lack of integrated sensors, or reliance on heterogeneous cell sources. In France, only very few initiatives have been undertaken in this field, highlighting the need to design a robust GFB-on-chip (GFBoC) model to remain competitive on the international stage.This PhD project aims to build technological basis for developing a physiologically relevant GFBoC. The work is structured around three main objectives. First, the molecular interactions within the glomerular basement membrane (GBM), with a particular emphasis on type IV collagen and its interactions with integrins, were studied through the development of an in vitro method dedicated to analyzing extracellular matrix proteins. Second, a microfluidic chip integrating electrodes was designed and fabricated to allow real-time, non-destructive monitoring of barrier permeability. A biocompatible alginate-based membrane was generated in situ, providing a thinner and more physiologically relevant alternative to the GBM. Finally, human induced pluripotent stem cells were explored as a source for differentiation into podocytes and glomerular endothelial cells.These results lay the foundation for a new generation of glomerulus-on-chip models combining bioengineering, microfluidics, and stem cell biology. This project illustrates the potential of OoC technologies to overcome the limitations of traditional models.