Directed Orchestration of Microfluidic Environments for guided Self-organisation

Descrizione del progetto

Un nuovo sistema microfluidico per la ricerca sui disturbi congeniti

Nonostante i progressi compiuti nella comprensione dei processi di gravidanza e nascita, resta ancora molto da esplorare in relazione alle anomalie congenite, i disturbi strutturali o funzionali che si verificano durante lo sviluppo del feto. Il progetto DOMES, finanziato dall’UE, si propone di identificare i fattori ambientali che contribuiscono alla manifestazione di tali disturbi. Più nello specifico, il progetto si concentrerà sullo sviluppo di un’innovativa piattaforma microfluidica di coltura cellulare 3D per lo studio dei fattori che si ripercuotono sui tessuti e l’organogenesi, nonché dei loro meccanismi patogeni. L’attenzione verterà sull’effetto di farmaci e interferenti endocrini sul dotto collettore e il loro impatto sulle malattie congenite dei reni.

Obiettivo

In Europe, 263 per 10,000 pregnancies are diagnosed with a fetal congenital anomaly. Congenital anomalies, also referred to as birth defects, are defined as structural or functional disorders that occur during fetal development and are inherited, and/or caused by environmental factors. Unfortunately, the link between environmental factors, such as drugs, toxins or other chemicals, and the manifestation of these multifactorial disorders is poorly understood. To identify environmental factors affecting tissue and organogenesis and study their pathogenic mechanisms, new 3D in vitro models with reliable and highly reproducible architecture are urgently needed. None of the current cell culture systems available can provide the controlled environment needed to sufficiently guide the self-organization process of stem cell-based 3D in vitro models. Our new microfluidic platform, DOMES, is the first of its kind, combining precise control over morphogenetic processes with standardized and user-friendly handling. In this project, we will exemplarily focus on congenital diseases of the kidney, in particular the collecting duct system. We will analyse on-chip the impact of specific environmental compounds, such as drugs and endocrine disruptors, on the branching morphogenesis of the collecting duct.
DOMES is a product family of microfluidic 3D cell culture chips which will allow the control and study not only of kidney organoids, but of other 3D cell models including lung, neural, gut organoids and embryoid bodies. This is the first instance of a cell culture platform allowing direct orchestration of the microfluidic environment for guiding self-organisation, symmetry breaking and organogenesis, and represents a paradigm shift in researchers ability to study development of organs and their congenital anomalies in vitro.