Building human innervated intestinal tissue to model and treat digestive diseases

Orateur : Maxime MAHE (The Enteric Nervous System in Gut and Brain Disorders, Université de Nantes)

The use of pluripotent stem cells offers great avenues to generate human tissues. The understanding of developmental processes and their translation to human pluripotent stem cells, had allow the field to move forward in understanding intestinal development and gastrointestinal diseases. I will describe our previous work which had focused on generating functional human intestinal organoids (HIOs) from embryonic stem cells and induced pluripotent stem cells. Building on this model, I will highlight the additional complexity we were able to engineer in order to gain insights into intestinal physiology and diseases. In this context, the development of human intestine with an enteric nervous system (ENS) represents a real opportunity to expand our knowledge into the effect of ENS on intestinal development and toward the understanding of pathophysiological processes leading to functional gastrointestinal neuropathies. As the complexity of the intestine is also tied to its environment, I will emphasize how we can use such models in integrating a luminal environment. Finally, I will delineate the forthcoming strategies that could be used to create a fully functional intestine that could pave the way for both precision and regenerative medicine.

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