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What are brain organoids?

Brain organoids are three-dimensional, tissue-like structures cultivated from stem cells that mimic important features of the developing brain. Brain organoids contain all the precursor cells of the brain as well as neurons and glial cells. They are used to study brain development processes, research diseases and test potential drugs for the treatment of neurological disorders. We use brain organoids to better understand the development and evolution of the neocortex in primates. They enable us to carry out these studies in vitro and thus reduce animal testing.

 

How are brain organoids produced?

We have developed a brain organoid protocol that allows us to cultivate organoids from different primate species. This allows us to produce brain organoids from humans, chimpanzees, rhesus monkeys and common marmosets. The advantage of this standardized protocol is that the same components and steps can be used for all primate species; only the timing of certain protocol steps varies depending on the species. Our protocol at JOVE.

 

Genetic modification of brain organoids

For our studies, we have to genetically modify brain organoids in order to investigate the function of genes. To do this, we modify the stem cells from which the brain organoids grow by removing genes or making them non-functional (knock-out) or adding genes (knock-in). However, as these stable genetic changes are very time-consuming, we prefer a different method: electroporation. Here, the organoids are modified directly, without the detour via the stem cells. We inject ring-shaped DNA, so-called plasmids, into the fluid-filled spaces of the brain organoids and apply a electric shock. As a result, the cells of the organoid take up the plasmids and the genes on the plasmid can be activated.