Pasteurdon 2022: brain organoids to study early brain aging

From stem cells, regulatory elements, nutrients and a lot of know-how from researchers, in two months it is possible to obtain a cerebral organoid a few millimeters long.

Under this name, which is reminiscent of a science fiction film, hides a research tool that is increasingly used to study the cellular and neuronal mechanisms involved in neurodegenerative diseases (note: Alzheimer’s for example).

These organoids come from pluripotent stem cells (IPS cells) which will differentiate and structure themselves to reproduce a micro-anatomy in vitro.

One of the advantages of these brain organoids is that they develop autonomously for about two months and they can be stored for a year or more in culture with an active metabolism. The 3D structuring makes it possible to be as close as possible to natural physiological conditions. This allows us to carry out in-depth analyzes over the long term and on a large number of samples to obtain significant results. explains Miria Ricchetti, Head of the Molecular Mechanisms of Pathological and Physiological Aging Unit at the Institut Pasteur.

Until now, the study of neurodegenerative diseases has come up against the fact that there is no optimal animal model. Indeed, the structure of the cerebral cortex of humans and rodents, the most widely used model, have important differences.

In addition, patients present with a very wide variability of symptoms and causes. With this new multidimensional cellular model, many themes can be explored with new possibilities such as the architecture and cellular interactions of a developing brain, neurodegeneration, infectious diseases that affect the brain, etc.

We have the possibility, for example, of labeling different molecules, of observing their interactions and their radiation, and of counting them cell by cell. It is also possible to study these organoids at different stages of development, on the whole of the organoid or in part. But what will really help us in understanding early aging is the comparison between organoids derived from cells derived from patients and those derived from healthy individuals. adds the researcher.

Although this model makes it possible to get closer to physiological conditions and to make a real leap forward, it has certain limits for understanding the mechanisms involved in brain aging.

Indeed, the organoids today are isolated and without interactions with other close or distant organs such as the intestines, for example, where links have now been demonstrated. But the scientific interest is such that this model will quickly improve. For example, the lack of vascularity in organoids is thought to be a limiting factor in their physical growth to scale up organs. Teams are working on this issue concludes Miria Ricchetti.

Many teams are working on IPS cells, differentiating them into several cell types (neural or intestinal cells, etc.), or even deriving different and complementary parts of the developing brain, which are then assembled.

These structures constitute even more advanced tools for certain studies, and open up more possibilities for the future.

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Pasteurdon 2022: brain organoids to study early brain aging

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