First-in-kind protocol for creating miniature artificial brains

Researchers worldwide can now create highly realistic brain cortical organoids.

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Thanks to a groundbreaking protocol developed by researchers at the University of California San Diego, scientists worldwide can now create highly realistic brain cortical organoids. These miniature artificial brains with functioning neural networks open up new possibilities for advanced research on autism, schizophrenia, and other neurological disorders characterized by altered electrical activity despite typical brain structure.

Alysson Muotri, Ph.D., director of the UC San Diego Sanford Stem Cell Institute (SSCI) Integrated Space Stem Cell Orbital Research Center, emphasizes the significant potential of this new technique. The SSCI is under the leadership of Dr. Catriona Jamieson, a prominent physician-scientist investigating how space influences cancer progression.

The groundbreaking technique enables the production of incredibly lifelike miniature versions of the human brain, matching the sophisticated neural network complexity found in fetal brains. Renowned professor Muotri, affiliated with UC San Diego School of Medicine, has successfully transported these brain replicas to the International Space Station (ISS) for experimentation under microgravity conditions.

While two other methods for generating brain organoids are available to the public, neither permits studying the brain’s electrical activity, in contrast, Muotri’s approach empowers researchers to analyze neural networks derived from the stem cells of individuals with diverse neurodevelopmental disorders.

“You no longer need to create different regions and assemble them together,” said Muotri, adding that his protocol allows different brain areas – like the cortex and midbrain – “to co-develop, as naturally observed in human development. I believe we will see many derivations of this protocol in the future for the study of different brain circuits.”

Brain cortical organoids are examined under an electronic microscope.
Brain cortical organoids are examined under an electronic microscope. Credit: UC San Diego Health Sciences

The development of “mini-brains” offers a valuable opportunity to test potential therapeutic drugs and gene therapies for safety and efficacy prior to patient use. Alysson Muotri, Ph.D., anticipates numerous adaptations of this protocol in the future for studying various brain circuits. As part of this effort, Muotri and researchers from the Federal University of Amazonas in Brazil are collaborating to investigate Amazonian tribal remedies for Alzheimer’s disease using diseased human brain organoids in space, bypassing traditional Earth-based mouse models.

A recent grant from Boryung, a prominent South Korean health care investment company, is set to propel a groundbreaking research project that will span diverse habitats from the Amazon rainforest to Dr. Muotri’s laboratory in California and, eventually, the International Space Station.

The brain organoids hold immense potential for disease modeling, understanding human consciousness, and conducting space-based experiments. In collaboration with NASA, Dr. Muotri sent brain organoids made from the stem cells of patients with Alzheimer’s disease and ALS (amyotrophic lateral sclerosis) to space. The findings from this pioneering venture eagerly anticipated and soon to be published, promise to advance our understanding in remarkable ways.

In studying the month-long mission’s payload, Muotri is poised to observe the effects of several years of disease progression due to microgravity, such as potential changes in protein production, signaling pathways, oxidative stress, and epigenetics.

“We’re hoping for novel findings – things researchers haven’t discovered before,” he said. “Nobody has sent such a model into space until now.”

Journal reference:

  1. Michael Q. Fitzgerald, Tiffany Chu, Francesca Puppo, Rebeca Blanch, Miguel Chillón, Shankar Subramaniam & Alysson R. Muotri. Generation of ‘semi-guided’ cortical organoids with complex neural oscillations. Nature Protocols, 2024; DOI: 10.1038/s41596-024-00994-0

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