It’s always gratifying when one of the projects you have funded starts to show promising results. It says your faith in the research and the researcher were well founded. But it’s also fun when the project you fund turns up some really cool findings and is picked as a top science story of the year.
That’s what happened with UC San Diego researcher Alysson Muotri’s work on growing brain organoids (tiny clumps of brain cells, created in a dish, that can mimic some of the properties of a real brain). His work, funded by yours truly, was chosen by Discover Magazine as one of the Top Ten Science stories of 2019.
For several years, researchers have been able to take stem cells and use them to make three dimensional structures called organoids. These are a kind of mini organ that scientists can then use to study what happens in the real thing. For example, creating kidney organoids to see how kidney disease develops in patients.
Scientists can do the same with brain cells, creating clumps
of cells that become a kind of miniature version of parts of the brain. These
organoids can’t do any of the complex things our brains do – such as thinking –
but they do serve as useful physical models for us to use in trying to develop
a deeper understanding of the brain.
Now Alysson Muotri and his team at UC San Diego – in
a study supported by two
grants from CIRM – have taken the science one step further, developing
brain organoids that allow us to measure the level of electrical activity they
generate, and then compare it to the electrical activity seen in the developing
brain of a fetus. That last sentence might cause some people to say “What?”, but
this is actually really cool science that could help us gain a deeper
understanding of how brains develop and come up with new ways to treat problems
in the brain caused by faulty circuitry, such as autism or schizophrenia.
The team developed new, more effective methods of growing
clusters of the different kinds of cells found in the brain. They then placed
them on a multi-electrode array, a kind of muffin tray that could measure
electrical impulses. As they fed the cells and increased the number of cells in
the trays they were able to measure changes in the electrical impulses they
gave off. The cells went from producing 3,000 spikes a minute to 300,000 spikes
a minute. This is the first time this level of activity has been achieved in a
cell-based laboratory model. But that’s not all.
When they further analyzed the activity of the organoids, they found there were some similarities to the activity seen in the brains of premature babies. For instance, both produced short bursts of activity, followed by a period of inactivity.
In a news
release Muotri says they were surprised by the finding:
“We couldn’t believe it at first — we
thought our electrodes were malfunctioning. Because the data were so striking,
I think many people were kind of skeptical about it, and understandably so.”
Muotri knows that this research –
published in the journal Cell Stem Cell – raises ethical issues and he is
quick to say that these organoids are nothing like a baby’s brain, that they differ
in several critical ways. The organoids are tiny, not just in size but also in
the numbers of cells involved. They also don’t have blood vessels to keep them
alive or help them grow and they don’t have any ability to think.
“They are far from being functionally
equivalent to a full cortex, even in a baby. In fact, we don’t yet have a way
to even measure consciousness or sentience.”
What these organoids do have is the ability to help us look
at the structure and activity of the brain in ways we never could before. In
the past researchers depended on mice or other animals to test new ideas or
therapies for human diseases or disorders. Because our brains are so different
than animal brains those approaches have had limited results. Just think about
how many treatments for Alzheimer’s looked promising in animal models but
failed completely in people.
These new organoids allow us to explore how new therapies
might work in the human brain, and hopefully increase our ability to develop
more effective treatments for conditions as varied as epilepsy and autism.