30 March 2017
The organoid revolution and DanStem contributions
’Organoids’ are miniature three-dimensional organ-like structures made in vitro from stem cells. Our capacity to make them and understand them has progressed tremendously since 2009. They enable scientists to bridge the gap between cells growing on the bottom of a petri dish and organs in animals.
DanStem has made contributions to the organoid adventure since its beginning and the Grapin-Botton lab has succeeded in producing pancreas organoids in vitro from dispersed embryonic organ stem cells (Greggio 2013). These organoids start from only a few cells that exchange information and also respond to signals from the gel they are grown into and from the components of the culture medium. These signals launch programs in the cells that enable them to divide to build organ mass, specialize into functional cell types and self-organize. This self-organization coordinates the cells in space to form ducts that will conduct the digestive enzymes, assemble enzyme-producing cells at the end of these ducts and hormone-secreting cells in the center. They already enabled the Grapin-Botton lab to study how organs form, using a simplified system and they are now developing a similar system from human stem cells that would allow to better understand how human organs form, a process that is secretly taking place in the womb. They are also trying to use this in vitro organ system to better understand how organs are affected by diseases.
Time to compare organoids from different organs to learn more about organ formation
Organoids are now pervading many laboratories to become a commonly used technique. The journal Development has thus recently published an excellent special issue with useful viewpoints comparing different organoid systems and deriving general conclusions. This should enable a better control over their production as well.
A physics approach to organoids
Organoids are small and notably simpler than real organs, and they can be grown in a dish which enables us to follow their development and every step on the way – from a few cells to a complex structure with thousands of cells. From the perspective of a physicist this simplification allows to find answers to some fundamental questions of life, how do cells rearrange themselves to form an organism, how do they know where to be, how do they change, how do they communicate? The organoids also provide a platform to customize what the cells grow in and hence one can find which environments allow the cells to prosper and rearrange. In our published review, we discuss different approaches to these questions, and the tools that can be used, such as computer modelling, controlling the growth environment and actively manipulating the cells by laser or magnetic fields.
In the long term, computational tools are expected to help us derive rules of organ formation and a platform to test the effect of perturbations in silico. The predictions from models could then be tested in organoids and ultimately in more complex in vivo systems, hopefully optimizing a discovery pipeline!
Dahl-Jensen, Svend* & Anne Grapin-Botton* (2017). The physics of organoids: a biophysical approach to understanding organogenesis. Development,144, 946-951, doi: 10.1242/dev.143693.