Project description
Promoting self-organisation for tissue engineering
Creating functional tissues with multiple cell types and three-dimensional architecture remains a major challenge in regenerative medicine. Without the ability to control cell behaviour, researchers struggle to produce complex tissues. Scientists are seeking new ways to overcome this challenge. The ERC-funded ORCHESTRATE project proposes a solution by promoting cells’ intrinsic capacity for self-organisation. By developing advanced cell culture platforms and using state-of-the-art biological methods, the project aims to develop in vitro models to test the hypothesis that by orchestrating self-organisation it is possible to create complex tissues, organs and even organisms with a high degree of reproducibility and in large numbers. The anticipated outcomes of the project will offer a promising solution to the challenge of creating functional tissues in regenerative medicine.
Objective
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.
Fields of science
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
6200 MD Maastricht
Netherlands