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#437957 Meet Assembloids, Mini Human Brains With ...
It’s not often that a twitching, snowman-shaped blob of 3D human tissue makes someone’s day.
But when Dr. Sergiu Pasca at Stanford University witnessed the tiny movement, he knew his lab had achieved something special. You see, the blob was evolved from three lab-grown chunks of human tissue: a mini-brain, mini-spinal cord, and mini-muscle. Each individual component, churned to eerie humanoid perfection inside bubbling incubators, is already a work of scientific genius. But Pasca took the extra step, marinating the three components together inside a soup of nutrients.
The result was a bizarre, Lego-like human tissue that replicates the basic circuits behind how we decide to move. Without external prompting, when churned together like ice cream, the three ingredients physically linked up into a fully functional circuit. The 3D mini-brain, through the information highway formed by the artificial spinal cord, was able to make the lab-grown muscle twitch on demand.
In other words, if you think isolated mini-brains—known formally as brain organoids—floating in a jar is creepy, upgrade your nightmares. The next big thing in probing the brain is assembloids—free-floating brain circuits—that now combine brain tissue with an external output.
The end goal isn’t to freak people out. Rather, it’s to recapitulate our nervous system, from input to output, inside the controlled environment of a Petri dish. An autonomous, living brain-spinal cord-muscle entity is an invaluable model for figuring out how our own brains direct the intricate muscle movements that allow us stay upright, walk, or type on a keyboard.
It’s the nexus toward more dexterous brain-machine interfaces, and a model to understand when brain-muscle connections fail—as in devastating conditions like Lou Gehrig’s disease or Parkinson’s, where people slowly lose muscle control due to the gradual death of neurons that control muscle function. Assembloids are a sort of “mini-me,” a workaround for testing potential treatments on a simple “replica” of a person rather than directly on a human.
From Organoids to Assembloids
The miniature snippet of the human nervous system has been a long time in the making.
It all started in 2014, when Dr. Madeleine Lancaster, then a post-doc at Stanford, grew a shockingly intricate 3D replica of human brain tissue inside a whirling incubator. Revolutionarily different than standard cell cultures, which grind up brain tissue to reconstruct as a flat network of cells, Lancaster’s 3D brain organoids were incredibly sophisticated in their recapitulation of the human brain during development. Subsequent studies further solidified their similarity to the developing brain of a fetus—not just in terms of neuron types, but also their connections and structure.
With the finding that these mini-brains sparked with electrical activity, bioethicists increasingly raised red flags that the blobs of human brain tissue—no larger than the size of a pea at most—could harbor the potential to develop a sense of awareness if further matured and with external input and output.
Despite these concerns, brain organoids became an instant hit. Because they’re made of human tissue—often taken from actual human patients and converted into stem-cell-like states—organoids harbor the same genetic makeup as their donors. This makes it possible to study perplexing conditions such as autism, schizophrenia, or other brain disorders in a dish. What’s more, because they’re grown in the lab, it’s possible to genetically edit the mini-brains to test potential genetic culprits in the search for a cure.
Yet mini-brains had an Achilles’ heel: not all were made the same. Rather, depending on the region of the brain that was reverse engineered, the cells had to be persuaded by different cocktails of chemical soups and maintained in isolation. It was a stark contrast to our own developing brains, where regions are connected through highways of neural networks and work in tandem.
Pasca faced the problem head-on. Betting on the brain’s self-assembling capacity, his team hypothesized that it might be possible to grow different mini-brains, each reflecting a different brain region, and have them fuse together into a synchronized band of neuron circuits to process information. Last year, his idea paid off.
In one mind-blowing study, his team grew two separate portions of the brain into blobs, one representing the cortex, the other a deeper part of the brain known to control reward and movement, called the striatum. Shockingly, when put together, the two blobs of human brain tissue fused into a functional couple, automatically establishing neural highways that resulted in one of the most sophisticated recapitulations of a human brain. Pasca crowned this tissue engineering crème-de-la-crème “assembloids,” a portmanteau between “assemble” and “organoids.”
“We have demonstrated that regionalized brain spheroids can be put together to form fused structures called brain assembloids,” said Pasca at the time.” [They] can then be used to investigate developmental processes that were previously inaccessible.”
And if that’s possible for wiring up a lab-grown brain, why wouldn’t it work for larger neural circuits?
Assembloids, Assemble
The new study is the fruition of that idea.
The team started with human skin cells, scraped off of eight healthy people, and transformed them into a stem-cell-like state, called iPSCs. These cells have long been touted as the breakthrough for personalized medical treatment, before each reflects the genetic makeup of its original host.
Using two separate cocktails, the team then generated mini-brains and mini-spinal cords using these iPSCs. The two components were placed together “in close proximity” for three days inside a lab incubator, gently floating around each other in an intricate dance. To the team’s surprise, under the microscope using tracers that glow in the dark, they saw highways of branches extending from one organoid to the other like arms in a tight embrace. When stimulated with electricity, the links fired up, suggesting that the connections weren’t just for show—they’re capable of transmitting information.
“We made the parts,” said Pasca, “but they knew how to put themselves together.”
Then came the ménage à trois. Once the mini-brain and spinal cord formed their double-decker ice cream scoop, the team overlaid them onto a layer of muscle cells—cultured separately into a human-like muscular structure. The end result was a somewhat bizarre and silly-looking snowman, made of three oddly-shaped spherical balls.
Yet against all odds, the brain-spinal cord assembly reached out to the lab-grown muscle. Using a variety of tools, including measuring muscle contraction, the team found that this utterly Frankenstein-like snowman was able to make the muscle component contract—in a way similar to how our muscles twitch when needed.
“Skeletal muscle doesn’t usually contract on its own,” said Pasca. “Seeing that first twitch in a lab dish immediately after cortical stimulation is something that’s not soon forgotten.”
When tested for longevity, the contraption lasted for up to 10 weeks without any sort of breakdown. Far from a one-shot wonder, the isolated circuit worked even better the longer each component was connected.
Pasca isn’t the first to give mini-brains an output channel. Last year, the queen of brain organoids, Lancaster, chopped up mature mini-brains into slices, which were then linked to muscle tissue through a cultured spinal cord. Assembloids are a step up, showing that it’s possible to automatically sew multiple nerve-linked structures together, such as brain and muscle, sans slicing.
The question is what happens when these assembloids become more sophisticated, edging ever closer to the inherent wiring that powers our movements. Pasca’s study targets outputs, but what about inputs? Can we wire input channels, such as retinal cells, to mini-brains that have a rudimentary visual cortex to process those examples? Learning, after all, depends on examples of our world, which are processed inside computational circuits and delivered as outputs—potentially, muscle contractions.
To be clear, few would argue that today’s mini-brains are capable of any sort of consciousness or awareness. But as mini-brains get increasingly more sophisticated, at what point can we consider them a sort of AI, capable of computation or even something that mimics thought? We don’t yet have an answer—but the debates are on.
Image Credit: christitzeimaging.com / Shutterstock.com Continue reading
#437918 Video Friday: These Robots Wish You ...
Video Friday is your weekly selection of awesome robotics videos, collected by your Automaton bloggers. We’ll also be posting a weekly calendar of upcoming robotics events for the next few months; here's what we have so far (send us your events!):
ICCR 2020 – December 26-29, 2020 – [Online]
HRI 2021 – March 8-11, 2021 – [Online]
RoboSoft 2021 – April 12-16, 2021 – [Online]
Let us know if you have suggestions for next week, and enjoy today's videos.
Look who’s baaaack: Jibo! After being sold (twice?), this pioneering social home robot (it was first announced back in 2014!) now belongs to NTT Disruption, which was described to us as the “disruptive company of NTT Group.” We are all for disruption, so this looks like a great new home for Jibo.
[ NTT Disruption ]
Thanks Ana!
FZI's Christmas Party was a bit of a challenge this year; good thing robots are totally competent to have a part on their own.
[ FZI ]
Thanks Arne!
Do you have a lonely dog that just wants a friend to watch cat videos on YouTube with? The Danish Technological Institute has a gift idea for you.
[ DTI ]
Thanks Samuel!
Once upon a time, not so far away, there was an elf who received a very special gift. Watch this heartwarming story. Happy Holidays from the Robotiq family to yours!
Of course, these elves are not now unemployed, they've instead moved over to toy design full time!
[ Robotiq ]
An elegant Christmas video from the Dynamics System Lab, make sure and watch through the very end for a little extra cheer.
[ Dynamic Systems Lab ]
Thanks Angela!
Usually I complain when robotics companies make holiday videos without any real robots in them, but this is pretty darn cute from Yaskawa this year.
[ Yaskawa ]
Here's our little christmas gift to the fans of strange dynamic behavior. The gyro will follow any given shape as soon as the tip touches its edge and the rotation is fast enough. The friction between tip and shape generates a tangential force, creating a moment such that the gyroscopic reaction pushes the tip towards the shape. The resulting normal force produces a moment that guides the tip along the shape's edge.
[ TUM ]
Happy Holidays from Fanuc!
Okay but why does there have to be an assembly line elf just to put in those little cranks?
[ Fanuc ]
Astrobotic's cute little CubeRover is at NASA busy not getting stuck in places.
[ Astrobotic ]
Team CoSTAR is sharing more of their work on subterranean robotic exploration.
[ CoSTAR ]
Skydio Autonomy Enterprise Foundation (AEF), a new software product that delivers advanced AI-powered capabilities to assist the pilot during tactical situational awareness scenarios and detailed industrial asset inspections. Designed for professionals, it offers an enterprise-caliber flight experience through the new Skydio Enterprise application.
[ Skydio ]
GITAI's S1 autonomous robot will conduct two experiments: IVA (Intra-Vehicular Activity) tasks such as switch and cable operations, and assembly of structures and panels to demonstrate its capability for ISA (In-Space Assembly) tasks. This video was recorded in the Nanoracks Bishop Airlock mock-up facility @GITAI Tokyo office.
[ GITAI ]
It's no Atlas, but this is some impressive dynamic balancing from iCub.
[ IIT ]
The Campaign to Stop Killer Robots and I don't agree on a lot of things, and I don't agree with a lot of the assumptions made in this video, either. But, here you go!
[ CSKR ]
I don't know much about this robot, but I love it.
[ Columbia ]
Most cable-suspended robots have a very well defined workspace, but you can increase that workspace by swinging them around. Wheee!
[ Laval ]
How you know your robot's got some skill: “to evaluate the performance in climbing over the step, we compared the R.L. result to the results of 12 students who attempted to find the best planning. The RL outperformed all the group, in terms of effort and time, both in continuous (joystick) and partition planning.”
[ Zarrouk Lab ]
In the Spring 2021 semester, mechanical engineering students taking MIT class 2.007, Design and Manufacturing I, will be able to participate in the class’ iconic final robot competition from the comfort of their own home. Whether they take the class virtually or semi-virtually, students will be sent a massive kit of tools and materials to build their own unique robot along with a “Home Alone” inspired game board for the final global competition.
[ MIT ]
Well, this thing is still around!
[ Moley Robotics ]
Manuel Ahumada wrote in to share this robotic Baby Yoda that he put together with a little bit of help from Intel's OpenBot software.
[ YouTube ]
Thanks Manuel!
Here's what Zoox has been working on for the past half-decade.
[ Zoox ] Continue reading