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Human 'mini-brains' in lab mimic development and disease

2 May 2017
Appeared in BioNews 898

New brain organoids have been created to show development of both healthy human brain cells and those associated with genetic disorders.

Using pluripotent stem cells, two studies reported in Nature last month have grown neurons into balls of cells called 'spheroids' that act as mini-brains. The first study created abnormally-functioning cells associated with Timothy syndrome, while the second developed a series of healthy neurons that naturally formed a brain circuit with electrical activity.

'The major conclusion is the confirmation/validation that the human pluripotent stem cells are plastic enough to generate the diversity of cells necessary to recreate human, early stages of neurodevelopment in a dish,' Dr Alysson Muotri from the University of California, San Diego and who was not involved in either study told The Scientist. 'Every neuroscientist working with early brain development will be excited by reading these articles.'

One study led by Dr Sergio Pasca and his team at the Stanford University, California is the first to fuse two brain region-specific 'cortical' spheroids. Using cells from three patients with Timothy Syndrome, cortical spheroids comprising around a million cells were developed to mimic neurons from both the deep brain and the cortex. In normal development, those cells located more deeply migrate towards those in the cortex to form a circuit enabling brain function, but here the deep-layer neurons advanced towards the cortical neurons in a dysfunctional way.

The spheroids 'help us see how brain development goes awry in patients with the different mutations linked to Timothy syndrome', said Dr Pasca.

The second study, lead by Dr Paola Arlotta at Harvard University, showed that it is possible to grow circuits of healthy neurons using similar methods. By modifying existing techniques, the research team developed spheroids of different types of healthy neurons and maintained them for over nine months, during which time they formed functional circuits that displayed brain-like electrical activity. Furthermore, the cells developed appropriately, growing dendritic spines -  the structures that receive electrical signals from other cells.

'This shows that the approach has much greater potential than we ever imagined,' said Dr Juergen Knoblich, of the Institute of Molecular Biotechnology in Austria, a pioneer in creating cerebral organoids who was not involved in either study. 'They've shown that if you keep [the mini-brain] growing for a long enough time, it will generate the whole repertoire of cells we see in the human brain.'

While these studies highlight the potential for brain organoids in research, a number of scientists have stressed that they are no substitute for the brain itself.

'It's important to keep such things in context. While useful, the networks formed in the lab cannot hope to match the complexity and power of a fully functioning human brain… A working brain is far more than a single network, and most diseases and disorders go way beyond the anomalous behaviour of small, isolated collections of cells, ' said Dr Dean Burnett, from the Cardiff Centre for Medical Education.

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