A tiny little tool ready to solve brain mysteries

IMAGE: Three-dimensional neural interface for cortical spheroids and engineered assemblages more

Credit: Northwestern University

A team of scientists, led by researchers at Northwestern University, Shirley Ryan AbilityLab and the University of Illinois at Chicago (UIC), has developed a novel technology promising to increase understanding of how brains develop, and offers answers about brain repair after neurotrauma and neurodegenerative diseases.

Their research is the first to combine the most sophisticated 3-D bioelectronic systems with highly advanced 3-D human neural cultures. The goal is to enable in-depth studies of how human brain circuits develop and repair themselves in vitro. The review is the cover story for the March 19 issue of Advances in science.

The cortical spheroids used in the study, similar to “micro-brains,” were derived from human-stimulated pluripotent cells. Reducing the 3-D neural interface system developed by the team, scientists were able to “create a mini-lab in a basin” designed specifically to study the micro-brains and to collect different types of data at the same time. Scientists introduced electrons to record electrical activity. They added tiny heating elements to keep the brain cultures warm or, in some cases, overheated the cultures to put pressure on them. They also introduced tiny probes – such as oxygen sensors and small LED lights – to perform optogenetic experiments. For example, they introduced genes into the cells that allowed them to control neural activity using light beats of different colors.

This platform then allowed scientists to perform complex studies of human material without directly involving humans or conducting aggressive experiments. In theory, anyone could donate a limited number of their cells (e.g., blood sample, skin biopsy). Scientists can then reprogram these cells to produce a tiny brain spheroid that shares a person’s genetic identity. The authors believe that by combining this technology with a personalized treatment method using brain cultures derived from human cells, they will be able to gain faster views and better novel interventions. generation.

“The advances inspired by this research will bring a new end to the way we study and understand the brain,” said Dr Colin Franz, Shirley Ryan AbilityLab, co-lead author of the paper. test of the cortical spheroids. “Now that the 3-D platform has been developed and tested, we will be able to conduct more focused studies of our patients recovering from neurological injuries. or fighting from neurodegenerative disease. ”

Yoonseok Park, a Northwestern University graduate and co-author, said, “This is just the beginning of an entirely new class of miniaturized 3-D bioelectronic systems that we can build to expand the potential of the regenerative medicine field. For. for example, the next generation of device will support the creation of even more complex cloud circuits from brain to muscle, and increasingly dynamic joints such as a beating heart. “

The conventional electrostatic precipitators for 2-D print cultures are flat and cannot conform to the complex structural designs found throughout nature, such as those found in the human brain. Furthermore, even with a 3-D system, it is extremely challenging to incorporate more than one type of material into a small 3-D structure. With this advancement, however, a whole class of 3-D bioelectronics devices have been adapted for the field of regenerative medicine.

“Now, with our small, soft 3-D electronics, the ability to build devices that are similar to the complex biological shapes found in the human body is finally capable, providing understanding much more complete on culture, “said John Rogers of Northwestern, who said he led technology development using technology similar to that found in phones and computers. “We no longer have to negotiate an action to achieve the optimal format for interfacing with our biology.”

As a next step, scientists will use the tools to better understand neurological disease, test drugs and treatments that have clinical potential, and compare different cell models derived from patients. This understanding will then allow a better grasp of individual differences that may be due to the wide variation of outcomes seen in neurological rehabilitation.

“As scientists, our goal is to make laboratory research as clinically relevant as possible,” said Kristen Cotton, research assistant at Dr. Franz’s laboratory. “This 3-D platform opens the door to new experiments, discoveries and scientific advances in regenerative neurorehabilitation therapy that have never been possible.”

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The work was supported by the National Institutes of Health Research Project Grant (R01) shared by John Rogers of Northwestern and Yonggang Huang, Dr Colin Franz of Shirley Ryan AbilityLab and John Finan of UIC. He was also supported by a generous philanthropic gift from the Belle Carnell family, who set up a neurorehabilitation rehabilitation fund for precision therapy in Dr. Franz’s laboratory.

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