July 2, 2019
Cerebral organoids are
artificially grown, 3D tissue cultures that resemble the human brain. Now,
researchers from Japan report functional neural networks derived from these
organoids in a study publishing June 27 in the journal Stem Cell Reports.
Although the organoids aren’t actually “thinking,” the researchers’ new tool —
which detects neural activity using organoids — could provide a method for
understanding human brain function.
“Because they can mimic
cerebral development, cerebral organoids can be used as a substitute for the
human brain to study complex developmental and neurological disorders,” says
corresponding author Jun Takahashi, a professor at Kyoto University.
However, these studies are
challenging, because current cerebral organoids lack desirable supporting
structures, such as blood vessels and surrounding tissues, Takahashi says.
Since researchers have a limited ability to assess the organoids’ neural
activities, it has also been difficult to comprehensively evaluate the function
of neuronal networks.
“In our study, we created a
new functional analysis tool to assess the comprehensive dynamic change of
network activity in a detected field, which reflected the activities of over
1,000 cells,” says first and co-corresponding author Hideya Sakaguchi, a
postdoctoral fellow at Kyoto University (currently at Salk Institute). “The
exciting thing about this study is that we were able to detect dynamic changes
in the calcium ion activity and visualize comprehensive cell activities.”
To generate the organoids,
Takahashi, Sakaguchi, and their team created a ball of pluripotent stem cells
that have the potential to differentiate into various body tissues. Then, they
placed the cells into a dish filled with culture medium that mimicked the
environment necessary for cerebral development. Using the organoids, the team
successfully visualized synchronized and non-synchronized activities in
networks and connections between individual neurons. The synchronized neural
activity can be the basis for various brain functions, including memory.
“We believe that our work
introduces the possibility of a broad assessment of human cell-derived neural
activity,” Sakaguchi says. The method could help researchers understand
processes by which information is encoded in the brain through the activity of
specific cell populations, as well as the fundamental mechanisms underlying
psychiatric diseases, he says.
While cerebral organoids
provide a means for studying the human brain, ethical concerns have been
previously raised regarding the neural function of cerebral organoids.
“Because cerebral organoids
mimic the developmental process, a concern is that they also have mental
activities such as consciousness in the future,” Sakaguchi says. “Some people
have referenced the famous ‘brains in a vat’ thought experiment proposed by
Hilary Putnam, that brains placed in a vat of life-sustaining liquid with
connection to a computer may have the same consciousness as human beings.”
However, Takahashi and
Sakaguchi believe that cerebral organoids are unlikely to develop consciousness
because they lack input from their surrounding environments.
“Consciousness requires
subjective experience, and cerebral organoids without sensory tissues will not
have sensory input and motor output,” Sakaguchi says. “However, if cerebral
organoids with an input and output system develop consciousness requiring moral
consideration, the basic and applied research of these cerebral organoids will
become a tremendous ethical challenge.”
In the future, applied
organoid research will likely explore three main areas — drug discovery,
modelling neuropsychiatric disorders, and regenerative medicine, Takahashi
says.
“Cerebral organoids can bring
great advances to pharmacological companies by replacing traditional animal
models and can also be used to model untreatable neural diseases,” he says.
“Using our method, it will be possible to analyze cell activity patterns in
brain functions to further explore these areas.”
Source:
Cell Press.
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