Though originally published in August, some exciting
neuroscience research is just starting to hit the news now. A lab in Austria has
created a cerebral organoid, a very small - less complex - embryonic human
brain from stem cells. Stem cells have already been used to make single neurons
(the cells that make up your brain), but the brain is not simply a pile of
neurons. Neurons are organized into different structures within the brain, as
well as specific layers in the cerebral cortex. Each structure and layer has a different
formation and therefore function. Because of its complexity and specificity, it
is important to have human brain
models instead of relying on lab animals.
The basic process is the same for any stem cell research. Stem cells are generalized (pluripotent) cells that have no destination yet. By bathing them in a bath of different nutrients and signaling chemicals, you can make them grow into whatever type of cell you like: skin cells, blood cells or nerve cells. In this study, a base of stem cells were bathed in a mix of neuronal chemical signals. After a few days, pluripotent tests were done to see if the cells were on their way to becoming neurons. Days 8-10 showed neuronal identity. Days 15-20 showed continuous neuronal tissue surrounding a fluid filled cavity reminiscent of the vesicles found in a human brain. The real test of this experiment’s success came at day 20, when tests for regional markers showed specific structures developing. Markers for regions like the hindbrain (which is not as pronounced in humans) shrunk while those for regions like the forebrain (which is larger in humans) grew. Markers for different layers of the brain even showed up, with their signature inside-out development. By two months, a 4mm diameter cerebral organoid with all the markers of a human embryonic brain had formed. Because of lack of a circulatory system, tissue in the center of the brain started to die out, and development stopped.
The basic process is the same for any stem cell research. Stem cells are generalized (pluripotent) cells that have no destination yet. By bathing them in a bath of different nutrients and signaling chemicals, you can make them grow into whatever type of cell you like: skin cells, blood cells or nerve cells. In this study, a base of stem cells were bathed in a mix of neuronal chemical signals. After a few days, pluripotent tests were done to see if the cells were on their way to becoming neurons. Days 8-10 showed neuronal identity. Days 15-20 showed continuous neuronal tissue surrounding a fluid filled cavity reminiscent of the vesicles found in a human brain. The real test of this experiment’s success came at day 20, when tests for regional markers showed specific structures developing. Markers for regions like the hindbrain (which is not as pronounced in humans) shrunk while those for regions like the forebrain (which is larger in humans) grew. Markers for different layers of the brain even showed up, with their signature inside-out development. By two months, a 4mm diameter cerebral organoid with all the markers of a human embryonic brain had formed. Because of lack of a circulatory system, tissue in the center of the brain started to die out, and development stopped.
This lab
did not stop there though. It wasn’t enough just to create the first cerebral
organoid, they had to put it to the test too. Microcephaly is a disorder
causing brains to stop growing before they reach full size, and can cause
serious mental defects. Genetic tests on mice have been unsuccessful because of
the specific differences in genes and brain structures. The Austrian team took
skin cells from a patient with severe Microcephaly, reprogrammed them back to
pluripotent stem like cells, then used the same technique to create a
‘personalized cerebral organioid’. Indeed, they found the patient’s cerebral
organoid was smaller than a normal one. By performing genetic and physical
tests on the organoid, they found the cause of the patients condition; a
genetic mutation causing certain developmental cells in the brain to stop
dividing too early. Armed with this knowledge, there is hope of early
intervention halting the progress of Microcephaly in future patients.
The
possibilities of uses for cerebral organoids are endless. Not only can they be
used to decode genetic disorders, but testing drugs on an organoid made from
non-embryonic stem cells is preferable to any current option both
scientifically and ethically. This is not to mention the possibilities of
personalized cerebral organoids. Have a headache? Let the doctor take some
flakes of your skin, and build you a mini-brain to see what the problem is. We
are of course a long way from
anything like this, but this progress is a huge leap in the right direction.
To read more about this research, here are articles from:
The Economist http://www.economist.com/news/science-and-technology/21584319-group-stem-cell-biologists-have-grown-organoid-resembles-brain
The Scientist http://www.the-scientist.com/?articles.view/articleNo/37262/title/Lab-Grown-Model-Brains/
Or read the original article from Nature:
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