Researchers from the University of California San Diego have developed a fast and low-cost method of creating human cortical organoids directly from primary cells. This new protocol will allow the researchers to better understand how our own brains work.
Human cortical organoids, or mini-brains derived directly from primary cells, gives scientists the best chance at doing effective research on the mysterious human brain. Research into human brain functions is currently limited by scientists' inability to experiment on live embryonic subjects due to ethical constraints.
'Brain-in-dish' research essential to breakthroughs
The fragile nature of the human brain also makes it difficult for research to be undertaken. While some animals provide the opportunity for live research, their brains only partially mimic the complexity of human neural networks.
The development of in vitro human organoids, which are three-dimensional simplified versions of an organ created from reprogrammed cells, has opened the doors to scientists being able to understand biological function and disease in greater detail.
“Cerebral organoids can form a variety of brain regions. They exhibit neurons that are functional and capable of electrical excitation. They resemble human cortical development at the gene expression levels.” said Alysson R. Muotri, Ph.D., director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.
Compressing process reduces time and costs
However developing human brain organoids is difficult, time-consuming and expensive. The process requires high levels of know-how and highly specialized equipment.
This new research enables scientists to rapidly reprogram individual somatic cells directly into cortical organoids from hundreds of individuals simultaneously. The novel method involves compressing and optimizing several steps in the existing process so that somatic cells are reprogrammed, expanded and stimulated to form cortical cells almost simultaneously.
“What we’ve done is establish a proof-of-principle protocol for a systematic, automated process to generate large numbers of brain organoids,” said Muotri.
“The potential uses are vast, including creating large brain organoid repositories and the discovery of causal genetic variants to human neurological conditions associated with several mutations of unknown significance, such as autism spectrum disorder. If we want to understand the variability in human cognition, this is the first step.”
The ‘brain-in-dish’ concept was used to determine that the Zika virus can cause severe birth defects. The process was also used in critical research that led to the repurposing of existing HIV drugs to treat a rare, inherited neurological disorder a well as to create Neanderthalic “mini-brains” that helped scientist understand our brains' evolution.
The research is published in the current online issue of the journal Stem Cells and Development.