Exeter, Devon UK • May 23, 2024 • VOL XII

Exeter, Devon UK • [date-today] • VOL XII
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Grow a Brain

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How do you make a mini-brain? Methods vary, but you want to start with some human pluripotent stem cells, stem cells that can split into multiple cells when you put them in the right environment – for some other organs, you can use adult stem cells too – and let them multiply. This means that you could take cells from your arm. Unlike in the past, when you had to form two-dimensional chains of cells, scientists have started raising stem cells free-floating in broth, where they aggregate and grow. They will start to form tiny balls, which you can look at through a microscope, and see… a teeny tiny brain! (roughly the size of a 14-week-old foetus’ brain) How do you maintain a brain without a body? Instead of blood, you give it oxygen, either via broth or by cutting them up and letting them multiply again.

lentil-sized organoids can help understand organs’ structures

These miniature brains are called organoids. Researchers have been using them to replicate human organs; we can’t produce full organs this way, and they lack certain important components, but lentil-sized organoids can help understand organs’ structures. Indeed, where they aren’t researching brains, scientists have been building tiny organs of all sorts: kidneys, lungs… Using organoids is simply easier than invasively dissecting a human and could help us understand diseases such as Epilepsy or Alzheimer’s, or, some imagine, to help regenerate damaged organs.

Brain organoids have already been used to research drugs for ‘Timothy Syndrome’, a rare illness linked to heart issues, malformations, Autism spectrum disorders. It is caused by an overactive calcium ion channel: organoids have allowed scientists to experiment with drugs that block this channel. It’s helped us figure out how ‘Zika’ viral infections work, and to find several compounds that can block infection. Those were tested, in a first instance, in two dimensions, and then a selection was tested in a 3D environment, on organoids.

The zika virus capsid (shell) protects genetic material. Source: wiki media

Another use for organoid brains is assembling models of mini brains. A research team at Stanford University used two separate dishes to grow tiny models of two separate, but adjacent, parts of the brain. They then put them into the same tube and, just like a full-size brain, the two parts knew to find each other and build enough connections to practically fuse overnight. Video recordings showed that elongated cells started jumping from one small part of the brain to the other! This still leaves the idea of tiny brains developing in labs feeling slightly Frankenstein-like.

However, the disadvantage of using organoids is that they’re much simpler than ‘real’, in-vivo, organs, but that they are still more complicated than the in-vitro systems used by scientists. This means that researchers are still finding out how accurately their findings transfer onto humans. Organoids lack important elements– such as immune cells– that would allow them to grow more, and that would allow them to mature past the age of cells found in foetuses.

That’s why the term ‘mini-brain’ is contested: science writer Philip Ball, whose stem cells were used to make a brain organoid, writes that “one can fairly say that the neurons “want” to make a brain but, lacking proper guidance, don’t quite know how to go about it”.

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