Descrizione del progetto
Promuovere l’auto-organizzazione per l’ingegneria dei tessuti
La creazione di tessuti funzionali con più tipi di cellule e un’architettura tridimensionale è ancora una sfida importante nella medicina rigenerativa. Senza la capacità di controllare il comportamento delle cellule, i ricercatori hanno difficoltà a produrre tessuti complessi. Gli scienziati stanno cercando nuovi modi per superare questa sfida. Il progetto ORCHESTRATE, finanziato dal CER, propone una soluzione promuovendo la capacità intrinseca di auto-organizzazione delle cellule. Sviluppando piattaforme avanzate di coltura cellulare e utilizzando metodi biologici all’avanguardia, il progetto intende sviluppare modelli in vitro per testare l’ipotesi secondo la quale, orchestrando l’auto-organizzazione, è possibile creare un gran numero di tessuti, organi e persino organismi complessi con un alto grado di riproducibilità. I risultati attesi del progetto offriranno una soluzione promettente alla sfida della creazione di tessuti funzionali nella medicina rigenerativa.
Obiettivo
A major challenge in regenerative medicine is to create phenotypic functioning tissues by controlling cell behaviour. We particularly lack the ability to form complex tissues composed of multiple cell types and with three-dimensional architecture, which are defining features of most tissues. We know that cells are conferred with the ability to choreograph their own development through self-organization. I hypothesize that if we actively promote this intrinsic capacity with new cell culture platforms, we can orchestrate self-organization to make complex tissues, organs, and even organisms with a high degree of reproducibility and in large numbers.
This proposal begins with the design and development of new cell culture platforms which will be used to test my hypothesis. Building upon our proprietary microfabrication and -fluidic technology, we will create advanced platforms that will control how cells aggregate and enable the application of biomolecules with spatial and temporal resolution to orchestrate self-organization. This technology will be transferred into three projects of increasing complexity and ambition: making in vitro models of pancreatic islets, the pituitary gland, and a mouse blastocyst. For each, we need to find the right conditions to enrich for desired phenotypes and functions, which means that we need quantitative read-outs. We will use state-of-the-art biological methods, including RNA-sequencing, to give us a holistic view of transcript expression and pathway activation, and in situ sequencing to allow us to pinpoint the expression of important phenotypic markers at a single cell level.
The anticipated outcomes of this proposal are three-fold: first, we will develop a new generation of cell culture platforms with integrated microfluidics; second, we will uncover new knowledge about how to orchestrate self-organization; and third, we will make in vitro models of pancreatic islets, pituitary glands, and mouse blastocysts.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-ADG - Advanced GrantIstituzione ospitante
6200 MD Maastricht
Paesi Bassi