There have been several successful attempts at creating cerebral organoids artificially in the lab. Now, a team of researchers in Japan have gone one step further and have demonstrated their artificial cerebral organoids have developed functional neural networks.
Since these cerebral organoids mimic development of brain tissue in humans, scientists can use the organoids as a substitute for the human brain and study neurological and developmental disorders. The organoids are of great value to pharmacological companies, who can replace animal models with the organoids for use in drug discovery. The organoids could also be developed to model currently untreatable diseases and neuropsychiatric disorders and are of great interest in the field of regenerative medicine.
However, there are limitations. While organoids have been created, they lack blood vessels and surrounding supportive tissues, so there are currently limitations on the size of the organoids. It has also been difficult to assess the function of neuronal networks.
The researchers at Kyoto University overcame many challenges but succeeded in creating the most advanced cerebral organoids yet. The organoids were grown from induced pluripotent stem cells (iPSCs) – Cells that have the ability to grow into any cell type in the body. The researchers created a ball of iPSCs which was placed in a culture medium to encourage cerebral development.
Over time the researchers detected synchronized neural activity, which is the basis of various brain functions such as memory, and non-synchronized activity. The researchers also visualized connections between individual neurons.
“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,” said corresponding author Hideya Sakaguchi. “The exciting thing about this study is that we were able to detect dynamic changes in calcium ion activity and visualize comprehensive cell activities.”
There are ethical concerns surrounding the creation of cerebral organoids or ‘mini brains’. At some point these organoids may develop functions such as consciousness, which would cause all manner of ethical problems. Jun Takahashi, Professor at the Kyoto University Center for iPS Cell Research and Application and corresponding author of the paper, does not believe that will be an issue as their cerebral organoids lack all sensory input and motor output which are required to develop consciousness.
“Using our method, it will be possible to analyze cell activity patterns in brain functions,” said Takahashi. That would allow untreatable diseases to be modeled and the organoids could replace traditional animal models for drug discovery.
Further information can be found in the paper – Self-Organized Synchronous Calcium Transients in a Cultured Human Neural Network Derived from Cerebral Organoids – which was recently published in Stem Cell Reports. DOI: 10.1016/j.stemcr.2019.05.029