The technique, published in Nature Protocols, enables advanced research on autism, schizophrenia, and other neurological disorders where brain structure is typical, but electrical activity is altered. This was highlighted by Alysson Muotri, Ph.D., corresponding author and director of the UC San Diego Sanford Stem Cell Institute (SSCI) Integrated Space Stem Cell Orbital Research Center. The SSCI is led by Dr. Catriona Jamieson, a physician-scientist focusing on how space affects cancer progression.
The method creates tiny replicas of the human brain that match "the complexity of the fetal brain's neural network," according to Muotri. Muotri, also a professor at UC San Diego School of Medicine, noted that these brain replicas have been studied on the International Space Station (ISS) under microgravity.
While two other protocols for brain organoids exist, they do not allow the study of the brain's electrical activity. Muotri's method enables research on neural networks from the stem cells of patients with neurodevelopmental conditions.
"You no longer need to create different regions and assemble them together," said Muotri. His protocol allows 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," he added.
These miniature brains can test therapeutic drugs and gene therapies before patient use, as well as screen for efficacy and side effects.
A collaborative project is underway with researchers at the Federal University of Amazonas in Manaus, Brazil, to study Amazonian tribal remedies for Alzheimer's disease using diseased human brain organoids in space.
A Humans in Space grant from Boryung, a South Korean health care investment company, supports this project. The research spans from the Amazon rainforest to Muotri's California lab and the International Space Station.
Other research possibilities include disease modeling, understanding human consciousness, and further space-based experiments. In March, Muotri, with NASA, sent brain organoids made from stem cells of patients with Alzheimer's and ALS to space. The payload returned in May, and results are under review.
Microgravity mimics accelerated aging, allowing Muotri to observe disease progression effects over the mission's month-long duration, including 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."
Research Report:Generation of 'semi-guided' cortical organoids with complex neural oscillations
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