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Scientists have developed a way to grow miniature versions of human organs; some of the weirdest organoids are the mini brains.

Hosted by: Olivia Gordon

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Sources:
https://www.nature.com/news/the-boom-in-mini-stomachs-brains-breasts-kidneys-and-more-1.18064
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https://www.quantamagazine.org/mini-brains-go-modular-20170809/
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https://www.nature.com/articles/d41586-018-04813-x ethics
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https://www.youtube.com/watch?v=EjiWRINEatQ&feature=youtu.be
https://www2.mrc-lmb.cam.ac.uk/groups/lancaster/
https://www2.mrc-lmb.cam.ac.uk/group-leaders/h-to-m/madeline-lancaster/
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Image Sources:
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https://commons.wikimedia.org/wiki/File:Blausen_0896_Ventricles_Brain.png
https://www.istockphoto.com/photo/brain-model-gm463463537-32704566
https://commons.wikimedia.org/wiki/File:BiggeggSH-SY5Y.jpg
https://commons.wikimedia.org/wiki/File:Cerebral_organoid_flowchart.png
https://commons.wikimedia.org/wiki/File:Zika-chain-colored.png
https://www.istockphoto.com/photo/green-lentils-gm689997322-127076295
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[♪INTRO].

It sounds like something out of a science fiction movie: miniature human organs that scientists can grow in a lab. But they exist — mini hearts, mini livers, mini lungs, mini guts, and even mini testes.

Scientists call them organoids, since they’re like organs. And the weirdest of them all is the mini brain, or cerebral organoid. It’s the one that raises the most questions for biologists and ethicists.

Even though they’re small, what’s amazing about organoids is that they replicate some of the 3D features of full-sized human organs. In the case of mini brains, that means developing ventricles, the fluid-filled spaces in the brain, and forming layers in the cortex, the outer part of the brain. This is a big deal for scientists because, in the past, they could never really get human brain cells to grow in more than just one layer.

Those cells also usually didn’t survive very long, and didn’t include many cell types like our brains actually do. Frankly, it had been hard to study how brains develop because rats and mice aren’t all that similar to us, and we can’t exactly do experiments on brain tissue from living people. The organoid breakthrough came in 2013, when a postdoc named Madeline Lancaster realized she had somehow created floating bits of brain tissue that had some structure to them.

And now we have the recipe down pat! Researchers start out with some stem cells, which have the potential to develop, or differentiate, into the cells of any organ they’re interested in growing. They feed them chemical signals to send them down the right path, and provide structural support — like a protein gel — so the cells will grow in 3D.

And they also do a bunch of stirring. Then, the cells take those cues and pretty much go to town, growing a lot like a brain would form from scratch. But, to be totally clear, these cells are forming basic structures and layers that can’t really do anything besides grow.

They’re not full-blown networks of firing neurons. Lancaster used cerebral organoids to learn new things about microcephaly, which is when a baby’s head is unusually small because its brain hasn’t developed normally. She took a microcephaly patient’s cells and used them to whip up a custom mini brain, which was smaller than normal.

It turned out that the patient’s stem cells were calling it quits early, developing into neurons instead of continuing to create many more cells. Other neuroscientists have done similar experiments to study autism. And they discovered that those patients tend to make more of a certain type of inhibitory neuron than normal.

And another group has used mini brains to study how the Zika virus wreaks havoc on fetuses during pregnancy. The researchers infected organoids with the virus, which killed off cells and kept cells from replicating. Now, as great as cerebral organoids have been for science so far, they’re not without flaws.

For one, they’re tiny. The biggest ones are made up of just 2-3 million cells, and are about the size of a lentil. Not exactly ready for prime time sci-fi.

An adult human brain, on the other hand, is crammed with about 50,000 times more cells. Part of this size limit is because we don’t know how to direct mini brains to make their own blood vessels yet. So if they get too big, the cells in the center don’t get enough nutrients and start to die.

Mini brains also don’t have all the right layers or cell types, especially when it comes to certain neuron-supporting cells called microglia. So cerebral organoids are still relatively simple clumps of tissue that are way different from an actual human brain. And we have to solve more technical hurdles before they can really help us study complex neurological diseases.

Plus, each mini brains grows a little bit differently. So it can be hard to do controlled experiments that produce clear results, including things like screening drugs to see what effects they have. Researchers are making headway, though, to get around some of these limitations.

For example, some scientists are growing multiple mini brains under different conditions to spur development of specific cell types. And then they put them together like Lego bricks to create more accurate models of brain development. And, recently in 2018, another group was able to transplant mini brains made from human cells into the brains of mice.

It wasn’t to make super mice or anything, but to try to give those mini brains a blood supply. And sure enough, the mice grew blood vessels that fed the organoids! So, we’re not there yet, but it’s pretty clear how ethicists already foresee some issues with mini brains down the road.

Because what happens if the brain blobs get to be so good that they can play a part in sensing things? Or stranger yet, have a kind of consciousness? No one really has answers yet, because what we’ve created are still just dishes of cells.

But as the technology advances, we’ll have to use our existing brains to figure out what to do about the mini ones. Thanks for watching this episode of SciShow! If you want to learn more about the biology and psychology of human brains, check out our sister channel SciShow Psych at youtube.com/scishowpsych. [♪OUTRO].