Tag Archives: Mini

Mini liver.

First lab-grown mini livers will allow researchers to study the organ, its diseases, and treatments

Researchers at the University of Pittsburgh (Pitt) School of Medicine have successfully grown miniature human livers in the lab.

Mini liver.

Photograph of rat liver, stripped of rat-specific cells and re-seeded with engineered human liver cells.
Image credits UPMC.

The genetically-modified diminutive organs are meant to be a test platform for scientists to simulate human liver disease progression and test therapies on. As a proof of concept, the Pitt team created one such miniliver that mimics non-alcoholic fatty liver disease (NAFLD).

DeLivering on demand

“This is the first time we can create genetically engineered human mini livers with a disease using stem cells in the lab,” said senior author Alejandro Soto-Gutierrez, Ph.D. and associate professor of pathology at Pitt’s School of Medicine.

The team creates their tiny livers by genetically-engineering human skin cells. These cells are programmed to simulate a certain disease, are then reverted back to their stem state, and then made to mature into fully-functional liver cells.

For the current paper, the team modified the cells to express a chemically activated switch that could clamp down the on SIRT1 gene (SIRT1 proteins are commonly associated with NAFLD). After turning these cells into liver cells, the researchers seeded them into rat livers (which were previously stripped of their own cells). The implanted cells matured into functional 3-D mini livers, with the blood vessels and other structural features of a normal organ.

The organ mimics non-alcoholic fatty liver disease (NAFLD), a condition which can lead to cirrhosis or even liver failure. NAFLD is quickly becoming the leading cause of chronic liver disease in the United States due to its association with obesity.

The team says that their mini livers offer researchers a unique platform to understand not just a disease and how it progresses, but also for the testing of therapeutics. It’s common for drugs to fail in clinical trials despite promising results in mice, they explain, citing the drug Resveratrol. Resveratrol acts on SIRT1, and it was effective in mouse models for the treatment of NAFLD but failed in human clinical trials.

“Mice aren’t humans,” Soto-Gutierrez said. “We are born with certain mutations, polymorphisms, that will predispose us to certain diseases, but you can’t study polymorphisms in mice, so making a mini customized human liver is advantageous.”

What sets the mini livers apart from ‘organoid‘ cultures — bundles of cells that self-assemble into simple versions of organs — is the presence of those structural features such as blood vessels, the team explains. However, they caution that the mini livers “lack the distinct zones of metabolic function” that normal livers have.

Once they fully matured, the team flipped the genetic switch they programmed into the cells (to suppress the SIRT1 gene) and the mini livers started to mimic the metabolic dysfunction observed in tissues NAFLD patients. Just like in the clinical trials, Resveratrol wasn’t effective on these livers, either.

However, the mini livers did allow the team to figure out what went wrong. Resveratrol boosts the activity of SIRT1 proteins not SIRT1 genes. When SIRT1 gene expression is suppressed, such as is the case with the micro livers and perhaps also NAFLD patients, there isn’t any protein to act on. The drug doesn’t work because it’s targeting the wrong step.

“That’s an insight that could only come from studying functional human tissue,” Soto-Gutierrez said.

“I imagine in the future we can make human livers where you can order what kind of function you want, or even enhance function.”

However, we’re a long way away from that point. These mini livers won’t be ready for clinical applications like transplantation anytime soon, Soto-Gutierrez adds.

The paper “Generation of Human Fatty Livers Using Custom-Engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 Metabolism” has been published in the journal Cell Metabolism.

Mini Cheetah.

MIT’s newest, diminutive robot can do backflips and outrun you in every single way

MIT’s newest robot is cute, tiny, modular, and could run rings around you.

Mini Cheetah.

*robotic cheetah noises*.
Image credits Bryce Vickmark.

Researchers at MIT have developed a ‘mini cheetah’ robot whose range of motion, they boast, would rival those of a champion gymnast. This four-legged robot (hardly more than a powerpack on legs) can move, bend, and swing its legs in a wide range of motions, which allows it to handle uneven terrain about twice as fast as a human, and even walk upside-down. The robot, its developers add, is also “virtually indestructible” at least as falling or slamming into stuff is concerned.

Skynet’s newest pet

The robot weighs in at a paltry 20 pounds, but don’t let its diminutive stature fool you. The mini cheetah can perform some really impressive tricks, even being able to perform a 360-degree backflip from a standing position. If kicked to the ground, or if it falls flat, the robot can quickly recover with what MIT’s press release describes as a “swift, kung-fu-like swing of its elbows.” Apparently, nobody at MIT has ever seen Terminator.

But, the mini cheetah isn’t just about daredevil moves — it’s also designed to be highly modular and dirt cheap (for a robot). Each of its four limbs is powered by three identical electric motors (one for each axis) that the team developed solely from off-the-shelf parts. Each motor (as well as most other parts) can be easily replaced in case of damage.

“You could put these parts together, almost like Legos,” says lead developer Benjamin Katz, a technical associate in MIT’s Department of Mechanical Engineering.

“A big part of why we built this robot is that it makes it so easy to experiment and just try crazy things, because the robot is super robust and doesn’t break easily, and if it does break, it’s easy and not very expensive to fix.”

The mini cheetah draws heavily from its much larger predecessor, Cheetah 3. The team specifically aimed to make it smaller, easier to repair, more dynamic, and cheaper so that they would create a platform on which more researchers can test movement algorithms. The modular layout also makes it highly customizable. In Cheetah 3, Katz explains, you had to “do a ton of redesign” to change or install any parts since “everything is super integrated”. In the mini cheetah, installing a new arm is as simple as adding some more motors.

“Eventually, I’m hoping we could have a robotic dog race through an obstacle course, where each team controls a mini cheetah with different algorithms, and we can see which strategy is more effective. That’s how you accelerate research.”

Each of the robot’s 12 motors is about the size of a Mason jar lid and comes with a gearbox that provides a 6:1 gear reduction, enabling the rotor to provide six times the torque that it normally would. A sensor permanently measures the angle and orientation of the motor and its associated limb, allowing the robot to keep tabs on its shape.

It’s also freaking adorable:

This lightweight, high-torque, low-inertia design allows the robot to execute fast, dynamic maneuvers and make high-force impacts on the ground without breaking any gears or limbs. The team tested their cheetah through the hallways of MIT’s Pappalardo Lab and along the slightly uneven ground of Killian Court. In both cases, it managed to move at around 5 miles (8 km) per hour. Your average human, for context, walks at about 3 miles per hour.

“The rate at which it can change forces on the ground is really fast,” Katz says. “When it’s running, its feet are only on the ground for something like 150 milliseconds at a time, during which a computer tells it to increase the force on the foot, then change it to balance, and then decrease that force really fast to lift up. So it can do really dynamic stuff, like jump in the air with every step, or run with two feet on the ground at a time. Most robots aren’t capable of doing this, so move much slower.”

They also wrote special code to direct the robot to twist and stretch, showcasing its range of motion and ability to rotate its limbs and joints while maintaining balance. The robot can also recover from unexpected impacts, and the team programmed it to automatically shut down when kicked to the ground. “It assumes something terrible has gone wrong,” Katz explains, “so it just turns off, and all the legs fly wherever they go.” When given a command to restart, the bot determines its orientation and performs a preprogrammed maneuver to pop itself back on all fours.

The team, funnily enough, also put a lot of effort into programming the bot to perform backflips.

“The first time we tried it, it miraculously worked,” Katz says.

“This is super exciting,” Kim adds. “Imagine Cheetah 3 doing a backflip — it would crash and probably destroy the treadmill. We could do this with the mini cheetah on a desktop.”

The team is building about 10 more mini cheetahs, which they plan to loan to other research groups. They’re also looking into instilling a (fittingly) very cat-like ability in their mini cheetahs, as well:

“We’re working now on a landing controller, the idea being that I want to be able to pick up the robot and toss it, and just have it land on its feet,” Katz says. “Say you wanted to throw the robot into the window of a building and have it go explore inside the building. You could do that.”

I have to admit, the idea of casually launching a robot out the window (there’s a word for that, by the way: defenestration) with complete disregard, and having it come back a few minutes later with its task complete, is hilarious to me. And probably why they will, eventually, learn to hate us.

Still, doom at the hands of our own creations is still a ways away, and not completely certain. Until then, the team will be presenting the mini cheetah’s design at the International Conference on Robotics and Automation, in May. No word on whether they’ll be giving these robots out at the conference, but if they are, I’m calling major dibs.