The Use of Pluripotent Stem Cells to Create Mini-Brains

A lot of researchers want to study the early development of the human brain. This is true because a lot of us still do not know the inner workings of it. Studying the early development of the brain could help us pinpoint exactly what causes neuropsychiatric disorders such as schizophrenia and autism, and many others.

However, that shifted since 2013 when some scientists were able to create a developing human brain just through the use of induced pluripotent stem cells. The stem cells were cultured in 3-D into pea size structures so that it will mimic the actual organ.

There were two studies that were published back on April 26. Paula Arlotta and her team created mini brains and Sergiu Pasca and his colleagues created neural spheroids. These are small balls of tissue that contains more than a million neurons each. Both of the researchers want to study the interactions of the different brain regions that are critical to the development of the cerebral cortex.

According to Alysson Muotri, a student that studies neurological diseases using induced pluripotent stem cells at the University of California, San Diego, the major validation that can be had from the two studies is that one can generate a human brain in a dish using genetically modified iPSCs.

In the past years prior to the two studies mentioned above, scientists are not able to pinpoint exactly how neuropsychiatric disorders came to be because it is highly influenced by an affected person’s genetics. That is why it has been so difficult to study such diseases in animal models.

Paula Arlotta said that because studying animal models will not yield anything tangible, the only way for researchers to truly find out what causes such disorders would be to create an actual human brain in a petri dish using induced pluripotent stem cells. You can only do so by using the stem cells that are extracted from the affected patient’s body so that it would replicate their own genome.


Sergiu Pasca and his colleagues, meanwhile, merged two spheroids. One contains GABAergic elements and the other one contains glutamergic factors. Pasca merged the two spheroids to see the interaction between the two.

Pasca’s experiment shows that creating a human forebrain that was derived from induced pluripotent stem cells are indeed possible in vitro. This can further the research of neuropsychiatric disorders.

Arlotta’s experiment, on the other hand, modified their created mini-brains in order for them to survive for so much longer- long enough for the brains to mature to the point of creating dendritic spines and other characteristics found in more developed brains.

To do this, Arlotta and her colleagues used single-cell mRNA sequencing to help characterize the different cell types that are present in the brain spheroids- both in 3 and 6-month periods. By the sixth month, the organoids would have created seven different neuronal cell types, including cortical and retinal cells, as well as even more different cell subtypes.

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