Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - ORCHESTRATE (Building complex life through self-organization: from organ to organism)

Teaser

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...

Summary

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.

Society stands to benefit greatly from regenerative medicine, which is a multidisciplinary field that combines biology, engineering and medicine to replace or regenerate organs and tissues. In particular, those suffering from chronic diseases may be presented with a cure for their condition in the form of a new organ or tissue. In ORCHESTRATE, we are developing technology and know-how to advance this field.

This proposal begins with the design and development of new cell culture platforms. Building upon our proprietary fabrication and microfluidic 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 focussing on different organs or organisms. For each, we need to find the right conditions to enrich for desired phenotypes and functions, which means that we need quantitative read-outs in the form of single cell information and imaging technology.

Work performed

We can highlight three main results:

1) We put significant effort into establishing an image acquisition platform for microscopic analyses of three-dimensional cell aggregates. We can image large quantities of aggregates in a partly automated manner. We are now working to optimize the subsequent analysis of the images.

2) We built multiple versions of cell culture platforms based on microfluidics. These allow us to both study and control cell behaviour at the same time. The platforms contain channels to control the exposure of cells to biomolecules with both spatial and temporal control.

3) We have developed an in vitro model of the adult pancreatic islet and we are investigating the influence of three cell types (alpha-, beta- and endothelial cells) on organization and function.

Final results

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.