3-D mini brains accelerate research for repairing brain function

December 6, 2017, Houston Methodist
Three-dimensional neural circuit "asteroid" composed of neurons (blue) and astrocytes (red and green) generated from human pluripotent stem cells. Credit: Robert Krencik and Jessy van Asperen

The Houston Methodist Research Institute is making mini brains from human stem cells that put researchers on a fast track to repair the nervous system after injury or disease of the brain and spinal cord.

Houston Methodist neuroscientist Robert Krencik, Ph.D., and his team have developed a new system to reduce the time it takes to grow these brain models, which will give them the ability to screen drugs and study what's behind disease-causing mutations more quickly. Their findings are described in an article titled "Systematic three-dimensional coculture rapidly recapitulates interactions between human neurons and astrocytes," in the Dec. 12 issue of Stem Cell Reports.

"We always felt like what we were doing in the lab was not precisely modeling how the cells act within the human brain," Krencik said. "So, for the first time, when we put these cells together systematically, they dramatically changed their morphological complexity, size and shape. They look like cells as you would see them within the human brain, so now we can study cells in the lab in a more natural environment."

And why is this important? Krencik says cells grown in traditional lab cultures are put on a flat petri dish, broken up and otherwise manipulated, disturbing their interactions. This results in not being able to reproduce the form, structure and developmental growth of the brain's cells in the lab, leading to very simplistic-looking and immature cells. In the , however, these cells are very complex-looking and interact in intricate ways with each other and the environment. New technologies are now focused on 3-D culture systems, but the exhaustive time for these studies is not feasible for accelerating discoveries.

"Normally, growing these 3-D mini brains takes months and years to develop," Krencik said. "We have new techniques to pre-mature the cells separately and then combine them, and we found that within a few weeks they're able to form mature interactions with each other. So, the length of time to get to that endpoint for studies is dramatically reduced with our system."

Krencik's lab focused on a star-shaped cell type called astrocytes, because they are a key factor in getting the brain's neurons to connect and talk to each other by helping to increase the number and strength of neuronal connections in the brain and . They are involved in most neural diseases and also are responsible for maintaining a healthy nervous system. With the model Krencik's team bioengineered, the incorporation of astrocytes accelerated the connections of the surrounding neurons.

Krencik's group is the first to specifically engineer astrocytes into these 3-D mini brains. By doing so, this led to the accelerated maturation of both the astrocytes and the surrounding neurons. Introducing them for the first time in this paper, he coined these bioengineered mini brains "asteroids" to distinguish them from other types of 3-D sphere cultures, known as organoids. Krencik's "asteroids" contain specific populations of astrocytes, whereas organoids have undefined numbers and types of cells.

"Using our system, we can generate mature astrocytes and have them interact intimately with neurons to a greater extent than has been done before," Krencik said. "Unlike other cells in the and in the rest of the body, astrocytes have unique properties in humans. It's thought they are partly responsible for the unique cognitive functions of humans and also may underlie aspects of human diseases, such as Alzheimer's and autism spectrum disorders."

Ultimately, Krencik is using these "asteroids" to form functional neural circuits that researchers can experimentally manipulate for developing treatments and deciphering what makes diseases tick. Krencik says they can make induced , commonly termed iPS , from any disease or patient and then form these mini brains to study the disease process, as well as screen therapeutic compounds on them to aid in the development of drugs. Within about five years, his goal is to use this system to develop clinical trials to improve or regenerate a person's impaired nervous system.

Explore further: Brain astrocytes linked to Alzheimer's disease

More information: Robert Krencik et al, Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes, Stem Cell Reports (2017). DOI: 10.1016/j.stemcr.2017.10.026

Related Stories

Brain astrocytes linked to Alzheimer's disease

November 20, 2017
Astrocytes, the supporting cells of the brain, could play a significant role in the pathogenesis of Alzheimer's disease (AD), according to a new study from the University of Eastern Finland. This is the first time researchers ...

Star-shaped brain cells orchestrate neural connections

November 8, 2017
Brains are made of more than a tangled net of neurons. Star-like cells called astrocytes diligently fill in the gaps between neural nets, each wrapping itself around thousands of neuronal connections called synapses. This ...

Inflamed support cells appear to contribute to some kinds of autism

October 18, 2017
Modeling the interplay between neurons and astrocytes derived from children with Autism Spectrum Disorder (ASD), researchers at University of California San Diego School of Medicine, with colleagues in Brazil, say innate ...

Scientists give star treatment to lesser-known cells crucial for brain development

August 16, 2017
After decades of relative neglect, star-shaped brain cells called astrocytes are finally getting their due. To gather insight into a critical aspect of brain development, a team of scientists examined the maturation of astrocytes ...

Researchers upend longstanding idea that astrocytes can't be differentiated from each other

July 14, 2017
From afar, the billions of stars in our galaxy look indistinguishable, just as the billions of star-shaped astrocytes in our brains appear the same as each other. But UCLA researchers have now revealed that astrocytes, a ...

A star is born: Lesser-known brain cell takes center stage

June 6, 2017
Neurons have long enjoyed the spotlight in neuroscience—and for good reason: they are incredibly important cellular actors. But, increasingly, star-shaped support cells called astrocytes are being seen as more than bit ...

Recommended for you

Protein droplets keep neurons at the ready and immune system in balance

August 15, 2018
Inside cells, where DNA is packed tightly in the nucleus and rigid proteins keep intricate transport systems on track, some molecules have a simpler way of establishing order. They can self-organize, find one another in crowded ...

Self-control develops gradually in adolescent brain

August 15, 2018
Different parts of the brain mature at different times, which may help to explain impulsive behaviors in adolescence, suggest researchers from Penn State and the University of Pittsburgh.

Research reveals that what we see is not always what we get

August 15, 2018
Researchers are helping to explain why some people anticipate and react to fast-moving objects much quicker than others.

New approach to treating chronic itch

August 15, 2018
Researchers at the University of Zurich have discovered a new approach to suppressing itch by targeting two receptors in the spinal cord with the right experimental drug. In a series of experiments in mice and dogs, they ...

Immune cells in the brain have surprising influence on sexual behavior

August 14, 2018
Researchers have found a surprising new explanation of how young brains are shaped for sexual behavior later in life.

Scientists pinpoint brain networks responsible for naming objects

August 14, 2018
Scientists at The University of Texas Health Science Center at Houston (UTHealth) have identified the brain networks that allow you to think of an object name and then verbalize that thought. The study appeared in the July ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.